SEARCH · PubMed Health

Results for “Neural Pathways”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 415 records · Page 23Linked to original sources

PubMed2006

Wnt signal pathways and neural stem cell differentiation.

Self-renewal, migration and differentiation of neural progenitor cells are controlled by a variety of pleiotropic signal molecules. Members of the morphogen family of Wnt molecules play a crucial role for developmental and repair mechanisms in the embryonic and adult nervous system. A strategy of disclosure of the role of different canonical (glycogen synthase kinase-3beta/beta-catenin-dependent) and noncanonical (Ca2+- and JNK-dependent) signal pathways for progenitor cell expansion and differentiations is illustrated at the example of the rat striatal progenitor cell line ST14A that is immortalized by stable retroviral transfection with a temperature-sensitive mutant of the SV40 large T antigen. A shift from permissive 33 degrees C to nonpermissive 39 degrees C leads to proliferation stop and start of differentiation into glial and neuronal cells. Investigation of expression of Wnts, Wnt receptors and Wnt-dependent signal pathway assay point to a stage-dependent involvement of canonical and noncanonical signaling in proliferation and differentiation of ST14A cells, whereby a mutual suppression of pathway activities is likely. Canonical Wnt molecules are not detected in proliferating and differentiating ST14A cells except Wnt2. The noncanonical Wnt molecules Wnt4, Wnt5a and Wnt11 are expressed in proliferating cells and increase during differentiation, whereas cellular beta-catenin decreases in the early phase and is restored in the late phase of differentiation. Accumulation of beta-catenin at the membrane in undifferentiated proliferating cells and its nuclear localization in nondividing undifferentiated cells under differentiation conditions argues for a distinct spatially regulated role of the molecule in the proliferation and early differentiation phase. Ca2+-dependent and JNK-dependent noncanonical Wnt signaling is not detected during differentiation of ST14A cells. Complete exploration of the role of Wnt pathways, for differentiation of the neural progenitor cells ST14A will require Wnt overexpression and exposure of ST14A cells to exogenous Wnts either with purified Wnts or by co-cultures with Wnt producers.

Animals↗

PubMed1991

The vasovagal response.

The vasovagal response is the development of inappropriate cardiac slowing and arteriolar dilatation. Vasovagal responses reflect autonomic neural changes: bradycardia results from sudden augmentation of efferent vagal activity, and hypotension results from sudden reduction or cessation of sympathetic activity and relaxation of arterial resistance vessels. Two different neural pathways are thought to be involved, one originating in the hypothalamus, the other in the heart. Direct hypothalamic activation of the medullary cardiovascular centres triggered by emotional stress or pain causes a vasovagal response (central type). The combination of a reduced central blood volume secondary to venous pooling or blood loss, and an increased inotropic state of the heart, may stimulate ventricular mechanoreceptors and provoke vasodilatation and bradycardia (peripheral type). Cardiovascular afferents originating from stretch receptors in various parts of the vascular tree sometimes induce opposite reflexes when compared with those from ventricular afferents. The depressor reflex involved in the peripheral type of vasovagal response originates in the heart itself and overrides normal baroreflex circulatory control; an antagonism between the control of volume and pressure on the filling side of the heart and the control system of arterial pressure becomes apparent. Vasovagal responses are not necessarily abnormal; the neural pathways involved in the vasovagal response are probably present in all healthy subjects who individually mainly differ in susceptibility.

Arterioles↗

PubMed1997

Trigeminal autonomic pathways involved in nociception-induced reflex cardiovascular responses.

Reflex cardiovascular responses elicited by noxious oro-facial stimulation are well known but the neural pathways that underlie trigeminal cardiovascular reflex reactions remain to be elucidated. In previous studies, we have shown that noxious electrical stimulation of the mandibular incisor in the anesthetized rat elicits increases in mean arterial blood pressure and heart rate (Allen, G.V., Barbrick, B. and Esser, M.J., Trigeminal parabrachial connections: possible pathway for nociception-induced cardiovascular reflex responses, Brain Res., 715 (1996) 125-135). In this study, microinjections of the presynaptic blocker, cobalt chloride, or the anesthetic agent, lidocaine, were made into selected brainstem sites to identify neural pathways that are involved in mediation of the reflex pressor responses. Ipsilateral and bilateral injections of chemical blocker into the dorsomedial spinal trigeminal nucleus, pars caudalis, lateral parabrachial nucleus and the rostral ventral lateral medulla/caudal A5 region attenuated the reflex cardiovascular response. Bilateral injections of cobalt chloride into the dorsomedial subnucleus caudalis resulted in 70-100% attenuation of the reflex pressor response. Bilateral injections of cobalt chloride and/or lidocaine into the lateral parabrachial nucleus or the rostral ventral lateral medulla/A5 region resulted in 43-57% and 44-100% attenuation of the reflex pressor response, respectively. There were no significant differences in the degree or duration of attenuation of the reflex pressor responses produced by cobalt chloride compared to that produced by lidocaine injections. The reflex pressor responses usually returned to baseline levels approximately 60 min following injection of the chemical blocker substance. The results indicate that noxious electrical stimulation of the mandibular incisor elicits a reflex increase in mean arterial blood pressure which is initially mediated in the dorsomedial spinal trigeminal nucleus, pars caudalis and is subsequently mediated in the lateral parabrachial nucleus and the rostral ventral lateral medulla/caudal A5 region.

Animals↗

PubMed1992

Developmental plasticity in neural circuits controlling birdsong: sexual differentiation and the neural basis of learning.

In many species of passerine songbirds, males learn their song during defined periods of life. Female song is often reduced or absent, as are the brain regions controlling song. Sexual differences in the brain arise because of the action of sex steroids, which trigger the formation of some neural pathways (especially the pathway from the higher vocal center to the robust nucleus) and prevent the atrophy of others in males. These neural changes occur during periods of developmental song learning and can recur during periods of learning in adult birds. The process of learning is correlated with major increases or decreases in the numbers of neurons in specific neuronal populations, suggesting that the formation or loss of specific neural pathways regulates the ability to learn. Species differences in sexual differentiation and learning allow informative cross-species comparisons of neural structure and behavior.

Animals↗

PubMed1989

Rhythms of serum melatonin in patients with spinal lesions at the cervical, thoracic or lumbar region.

The neural pathway essential for the diurnal rhythm of serum melatonin was studied in humans. Blood samples from 17 patients with chronic lesions of cervical (n = 8), low thoracic or lumbar (n = 9) spinal cord were collected at 0200, 0400, 1000 and 1400 h of their normal light-dark cycle. Blood samples were also collected from eight control subjects at 0200 and 1400 h. No special treatment of food, drug or photoperiod was implemented. Serum melatonin was extracted by dichloromethane and determined by radioimmunoassay. In patients with cervical spinal lesions (C3-C7), it was found that serum melatonin levels were low and no diurnal rhythm was observed. Conversely, diurnal rhythm of circulating melatonin with significantly higher levels (P less than 0.01) in the dark period were observed in individuals with injuries at the low thoracic or lumbar regions (T9-L2). In the second experiment, blood samples from two other patients were collected for three consecutive days during acute period of spinal injuries (cervical or upper thoracic region) and serum melatonin concentrations were determined. Again, there were low levels of serum melatonin with no observable diurnal rhythm in the patient with cervical lesion (C4-5). However, diurnal rhythms were maintained with high levels in the dark period in the patient with upper thoracic spinal (T2-3) transection. Our data suggest that the cervical region of the spinal cord is part of the neural pathway essential for the diurnal rhythm of pineal melatonin secretion in human beings.

Adult↗

PubMed1990

Role of gastrin in bombesin-stimulated somatostatin release.

The intermediary pathways in the bombesin-induced somatostatin release were examined in isolated perfused rat stomach obtained from male rats that were fasted overnight. The stomachs were perfused by way of the celiac artery. On coinfusion of 1.0 mumol/L tetrodotoxin and 1 nmol/L bombesin, a significant depression in release of somatostatin was observed compared with that observed with bombesin alone. The 5-minute integrated somatostatin response after treatment with tetrodotoxin and bombesin was 173% +/- 14% of basal, which was significantly lower than that observed with bombesin alone (394% +/- 59% of basal, P less than 0.05) but significantly higher than that observed with medium-199 alone (95% +/- 7% of basal, P less than 0.05); this indicated that approximately 70% of the bombesin-stimulated somatostatin release was indirectly mediated through neural pathways, while a significant (approximately 30%) segment of it was mediated by nonneural mechanisms. To test if the 30% somatostatin release was secondary to gastrin release in response to bombesin, gastrin antiserum and bombesin (1 nmol/L) were coadministrated in the presence or absence of tetrodotoxin (1 mumol/L). Gastrin antiserum alone did not significantly affect basal release of somatostatin but caused a significant inhibition (approximately 23%) of bombesin-provoked somatostatin release. Coadministration of gastrin antiserum and tetrodotoxin attenuated bombesin-stimulated somatostatin release. Gastrin (1 mumol/L) alone significantly stimulated somatostatin release (150% +/- 10% of basal), which was completely attenuated in the presence of gastrin antiserum. Tetrodotoxin did not affect bombesin-elicited gastrin release, confirming that bombesin-stimulated gastrin release was directly mediated. To determine the nature of the neural pathways mediating the bombesin-induced somatostatin release, atropine (100 nmol/L) was used. Atropine inhibited bombesin-induced somatostatin release to the same extent as tetrodotoxin, indicating that cholinergic pathways mediated bombesin-induced somatostatin release. These results show that almost all the somatostatin response to bombesin is indirectly mediated, and is composed of a major neural (cholinergic) and a minor nonneural pathway. The nonneural mechanism appears to be contributed primarily by gastrin released in response to bombesin, which apparently has a short paracrine positive feedback effect on somatostatin release.

Animals↗

PubMed1999

Brain magnetic resonance imaging of structural abnormalities in bipolar disorder.

BACKGROUND: The neuropathogenesis of bipolar disorder remains poorly described. Previous work suggests that patients with bipolar disorder may have abnormalities in neural pathways that are hypothesized to modulate human mood states. We examined differences in brain structural volumes associated with these pathways between patients with bipolar disorder hospitalized with mania and healthy community volunteers. METHODS: Twenty-four patients with bipolar disorder and mania were recruited from hospital admission records. Twenty-two healthy volunteers were recruited from the community who were similar to the patients in age, sex, race, height, handedness, and education. All subjects were scanned using a 3-dimensional radio-frequency-spoiled Fourier acquired steady state acquisition sequence on a 1.5-T magnetic resonance imaging scanner. Scans were analyzed using commercial software. Prefrontal, thalamic, hippocampal, amygdala, pallidal, and striatal volumetric measurements were compared between the 2 groups. RESULTS: Patients with bipolar disorder demonstrated a significant (A = 0.64; F6,37 = 3.4; P = .009) overall difference in structural volumes in these regions compared with controls. In particular, the amygdala was enlarged in the patients. Brain structural volumes were not significantly associated with duration of illness, prior medication exposure, number of previous hospital admissions, or duration of substance abuse. Separating patients into first-episode (n = 12) and multiple-episode (n = 12) subgroups revealed no significant differences in any structure (P>.10). CONCLUSION: Patients with bipolar disorder exhibit structural abnormalities in neural pathways thought to modulate human mood.

Adolescent↗

PubMed2005

Involvement of the bed nucleus of the stria terminalis activated by the central nucleus of the amygdala in the negative affective component of morphine withdrawal in rats.

The central nucleus of the amygdala (Ce) and the bed nucleus of the stria terminalis (BST) are key structures of the extended amygdala, which is suggested to be involved in drug addiction and reward. We have previously reported that the Ce plays a crucial role in the negative affective component of morphine withdrawal. In the present study, we examined the involvement of the neural pathway between the Ce and the BST in the negative affective component of morphine withdrawal in rats. Rats were rendered morphine dependent by s.c. implantation of a 75-mg morphine pellet for 3 days, and morphine withdrawal was precipitated by an i.p. injection of naloxone (0.3 mg/kg). In the place-conditioning paradigm, discrete bilateral excitotoxic lesions of the Ce or the BST significantly reduced naloxone-precipitated morphine withdrawal-induced conditioned place aversion. On the other hand, they had little effect on morphine withdrawal-induced somatic signs. In an immunohistochemical study for c-Fos protein, naloxone-precipitated morphine withdrawal dramatically induced c-Fos-immunoreactive neurons in the capsular part of the Ce, and the lateral and medial divisions of the BST. Bilateral excitotoxic lesion of the Ce reduced the number of morphine withdrawal-induced c-Fos-immunoreactive neurons in the lateral and medial BST, with significant decreases in the posterior, ventral and juxtacapsular parts of lateral division, and anterior part of the medial division, but not in the ventral part of the medial division of the BST. On the other hand, bilateral excitotoxic lesion of the BST had no effect on such c-Fos induction within the capsular part, nor the ventral and medial divisions of the Ce. These results suggest that activation of the BST mediated through the neural pathway from the Ce contributes to the negative affective component of morphine withdrawal.

Amygdala↗

PubMed1986

[Importance of intraoperative monitoring of ABR and compound action potential of the eighth cranial nerve during microvascular decompression surgery].

An intraoperative recording of a direct compound action potential of the 8th cranial nerve with pre, intra and postoperative monitorings of auditory brainstem evoked response (ABR) was carried out for the purpose of clarifying mechanism and prevention of postoperative hearing dysfunction following microvascular decompression surgery as a treatment for hyperdysfunction syndrome of cranial nerves. In 221 patients with hemifacial spasm and tic douloureux out of 510 patients operated on by microvascular decompression surgery, ABR was monitored before, during and after surgery and furthermore, in the recent 94 patients among them, an intraoperative direct recording of a compound action potential of the acoustic nerve was performed simultaneously. Among these 94 patients, postoperative mild hearing dysfunction was encountered in 11 patients and severe reduction of hearing acuity in 2. As a result of our studies of monitoring action potential of the 8th cranial nerve and ABR, the following conclusions were drawn. When a latency of component V of ABR was delayed by more than 1.5-2.0 msec during surgery, and delay of latency of main negative peak (N1) of an action potential of the acoustic nerve exceeded by more than 1.0 msec, the occurrence rate of postoperative hearing dysfunction became positively high. There were two different types of changes in both ABR and action potentials; one type was a delay of an action potential in combination with that of ABR latencies and the other one was merely a delay in ABR components without following a remarkable change in action potentials. The former change might due to be an insult of whole neural pathways of the 8th cranial nerve including a cochlear nucleus and the latter change may due to be functional changes of the structures proximal to the cochlear nucleus. The delay of latencies in ABR and action potentials could be imposed either by a traction of the 8th cranial nerve or by a compression of the region of cochlear nucleus by a blain spatula as well as a vascular insufficiency of the tiny vessels which supplied these neural structures. To avoid the surgical insult to the acoustic nerve itself and more proximal neural pathways, the traction of any neural structures by a brain spatula should be lasted less than 5 minutes with more than 2 minutes intervals when judged from the results of our monitoring studies and the pressure of the compression on the cerebellar cortex is much preferable to be less than 20 mmHg for the safety throughout whole surgical procedures.

Adult↗

PubMed2004

Differential regulation of the mitochondrial and death receptor pathways in neural stem cells.

Despite an increasing interest in neural stem cell (NSC) research, relatively little is known about the biochemical regulation of cell death pathways in these cells. We demonstrate here, using murine-derived multipotent C17.2 NSCs, that cells undergo mitochondria-mediated cell death in response to apoptotic stimuli such as oxidative stress induced by 2,3-dimethoxy-1,4-naphthoquinone (DMNQ). In particular, treated cells exhibited apoptotic features, including Bax translocation, cytochrome c release, activation of caspase-9 and -3, chromatin condensation and DNA fragmentation. Although C17.2 cells possess the Fas receptor and express procaspase-8, agonistic Fas mAb treatment failed to induce apoptosis. Fas treatment activated the extracellular signal-regulated protein kinase (ERK) pathway, which may have an antiapoptotic as well as a growth stimulating role. Combined, our findings indicate that while NSCs are sensitive to cytotoxic stimuli that involve an engagement of mitochondria, Fas treatment does not induce death and may have an alternative role.

Amino Acid Chloromethyl Ketones↗

PubMed1989

Intramural neural control of opossum sphincter of Oddi.

We evaluated the intramural neural control of the opossum sphincter of Oddi (SO) in an in vitro preparation. Force transducers were used to record contractions at four sites along the sphincter segment. To stimulate intramural nerves, 10- to 120-s trains of pulses (4-10 V amplitude, 0.5 ms duration, and 5 Hz frequency) were delivered to one of three electrode pairs implanted along the SO. Electrical stimulation in the proximal, mid, or distal SO elicited phasic contractions that invariably originated in the proximal SO and propagated antegrade along the entire length of the sphincter segment. Stimulus-evoked contractions resembled spontaneous antegrade peristaltic contractions, but occurred at a higher rate (12-20/min). Atropine completely blocked this excitatory response to nerve stimulation. After atropine, nerve stimulation in the proximal, mid, or distal SO abolished spontaneous contractions at and distal to the site of stimulation for the duration of the stimulus. The inhibitory response to nerve stimulation was completely blocked by tetrodotoxin but was unaffected by phenoxybenzamine, tolazoline, or propranolol. We conclude that 1) the opossum SO is innervated by intramural cholinergic excitatory nerves and nonadrenergic noncholinergic inhibitory nerves; 2) cholinergic excitatory nerves are organized in ascending neural pathways, whereas nonadrenergic noncholinergic inhibitory nerves descend along the length of the SO; and 3) these neural pathways may modulate SO peristalsis in vivo and participate in ascending excitatory and descending inhibitory reflexes.

Ampulla of Vater↗

PubMed2003

A conserved role for the MEK signalling pathway in neural tissue specification and posteriorisation in the invertebrate chordate, the ascidian Ciona intestinalis.

Ascidians are invertebrate chordates with a larval body plan similar to that of vertebrates. The ascidian larval CNS is divided along the anteroposterior axis into sensory vesicle, neck, visceral ganglion and tail nerve cord. The anterior part of the sensory vesicle comes from the a-line animal blastomeres, whereas the remaining CNS is largely derived from the A-line vegetal blastomeres. We have analysed the role of the Ras/MEK/ERK signalling pathway in the formation of the larval CNS in the ascidian, Ciona intestinalis. We show evidence that this pathway is required, during the cleavage stages, for the acquisition of: (1) neural fates in otherwise epidermal cells (in a-line cells); and (2) the posterior identity of tail nerve cord precursors that otherwise adopt a more anterior neural character (in A-line cells). Altogether, the MEK signalling pathway appears to play evolutionary conserved roles in these processes in ascidians and vertebrates, suggesting that this may represent an ancestral chordate strategy.

Animals↗

PubMed1970

Auditory frequency-following response: neural or artifact?

An electrical response which reproduces the waveform and frequency of the sound stimulus can be recorded from the central neural pathway for audition. Controversy has existed for some years over whether this frequency-following response (FFR) is neural or an artifact such as remote pickup of the cochlear microphonic or cross talk in the recording system. Two experiments resolve this issue by demonstrating that the frequency-following response depends upon functionally intact neural pathways. The frequency-following response, as well as auditory evoked potentials, is abolished by section of the eighth nerve; it is reversibly abolished by cooling of the cochlear nucleus.

Cochlear Nerve↗

PubMed2001

The Wnt/beta-catenin pathway posteriorizes neural tissue in Xenopus by an indirect mechanism requiring FGF signalling.

In order to identify factors involved in posteriorization of the central nervous system, we undertook a functional screen in Xenopus animal cap explants which involved coinjecting noggin RNA together with pools of RNA from a chick somite cDNA library. In the course of this screen, we isolated a clone encoding a truncated form of beta-catenin, which induced posterior neural and dorsal mesodermal markers when coinjected with noggin in animal caps. Similar results were obtained with Xwnt-8 and Xwnt-3a, suggesting that these effects are a consequence of activating the canonical Wnt signalling pathway. To investigate whether the activation of posterior neural markers requires mesoderm induction, we performed experiments using a chimeric inducible form of beta-catenin. Activation of this protein during blastula stages resulted in the induction of both posterior neural and mesodermal markers, while activation during gastrula stages induced only posterior neural markers. We show that this posteriorizing activity occurs by an indirect and noncell-autonomous mechanism requiring FGF signalling.

Animals↗

PubMed2001

The relationship between propagated contractions and pseudoaffective changes in blood pressure in response to intestinal distension.

We investigated the relationship between changes in small intestinal motility and changes in blood pressure and heart rate in response to intestinal distension. Rats were maintained under stable anaesthesia with alpha-chloralose, and jejunal motility, blood pressure and heart rate were recorded. Pressure changes during propagated contractions of the circular muscle were recorded in the jejunum when the intraluminal pressure was maintained at 10 mmHg. Raising the pressure in 10 mmHg increments from 10 mmHg to 40 mmHg increased the frequency of propagated contractions from 0.30 +/- 0.06 min-1 (mean +/- SEM) to 1.29 +/- 0.09 per min. In contrast, amplitudes of contractions above baseline pressure decreased from 19.5 +/- 0.6 mmHg to 7.8 +/- 0.5 mmHg. Simultaneously, blood pressure and heart rate were both increased. Pretreatment of rats with capsaicin, or severing the mesenteric nerves acutely, prevented these cardiovascular responses, but did not influence the changes in propagated activity caused by distension. Propagated contractions were blocked by hexamethonium (10 mg kg-1, intravenously [i.v.]) and by local application of 2% lidocaine, but propulsion was unchanged by hyoscine (1 mg kg-1, i.v.). Phentolamine (1 mg kg-1, i.v.) increased the frequency of propagated contractions. The methods described in this work allow the effects of drugs on intrinsic intestinal reflexes to be distinguished from their effects on extra-intestinal, pseudoaffective reflexes. In addition, unlike other experiments using anaesthetized rats, blood pressure increased in response to distension, as it does in mammals that are not anaesthetized. The experiments demonstrate that the neural pathways for propagated contractions that rely on intrinsic nerve circuits, including intrinsic primary afferent neurones, and the neural pathways for extrinsic reflexes that signal pain or discomfort in the intestine, which involve capsaicin-sensitive spinal afferent neurones, are independent.

Adrenergic alpha-Antagonists↗

PubMed1996

Novel estrogen feedback sites associated with stress-induced suppression of luteinizing hormone secretion in female rats.

1. The fasting-induced suppression of LH secretion is totally dependent on steroidal milieu because the suppression is observed only in intact or ovariectomized estrogen-primed rats but not in ovariectomized animals. The following neural pathway mediating fasting-induced suppression of LH secretion has been suggested by a series of experiment: A neural signal emanating from the stomach during fasting reaches the medulla oblongata via afferent vagal nerve so as to activate the noradrenergic system projecting to the PVN: this results in an increased CRH release, and in turn the suppression of the LHRH release and then LH release. Estrogen seems to activate the neural pathway by acting on somewhere in the pathway. 2. We found that the paraventricular nucleus of the hypothalamus (PVN) and A2 region of the medulla oblongata is the estrogen feedback sites associated the dependence of the fasting-induced suppression of LH secretion on estrogen. The estrogen feedback action on the PVN does not involve an increase in norepinephrine release in the PVN. In addition, we also found that estrogen receptors are increased in the PVN and A2 region by acute fasting. Therefore, the following hypothesis is proposed: fasting first induces an transient increase in the activity of noradrenergic system at the beginning of the first dark phase after the food deprivation; this activation results in an increase in estrogen receptors in the PVN and A2 region; the increase in estrogen receptors leads to an increase in the sensitivity of noradrenergic systems to the neural inputs associated with fasting to these nuclei. 3. The response of the reproductive activity to various external stimuli including stress is modulated by ovarian steroids. The estrogen feedback action on the PVN and A2 is totally different from the so-called "negative feedback action" of estrogen that is for monitoring the ovarian condition. The novel estrogen feedback action may alter the response of neurons regulating gonadal axis to the signal associated with environmental cues such as stress.

Animals↗

PubMed1997

[Regrowth of central respiratory pathways in neural graft. From research tool on the axonal regeneration to a strategy of post-traumatic reparation].

This review focuses on the regrowth of respiratory pathways after nerve grafting within the central nervous system of the adult rat. After a general presentation of the background and of the grafting procedure, we summarize our nerve grafting results of while it is now well established that severed axons of adult central neurons can regenerate within segments of peripheral nerve partially implanted within the brain or spinal cord, the functional properties of the regenerating neurons remain generally unknown. With a view to assessing the extent to which the functional capacities of central neurons can be maintained after axonal regeneration, we have carried out experiments on central respiratory neurons which are a good example of a highly organized neuronal network with characteristic patterns of spontaneous discharge. We have shown that axonal regrowth of central respiratory neurons was successfully induced in blind-ended medullary and spinal autografts implanted respectively within the respiratory centers of the medulla oblongata and within the cervical spinal cord at the level of descending respiratory pathways. The grafts consisted of true "supplementary nerve" in which normal afferent and efferent respiratory pathways were confirmed by recording respiratory unitary discharges from teased fibers within the grafts. The efferent discharges reflected the activity of central respiratory neurons that had regenerated axons within the grafts: these neurons manifested spontaneous activity and normal responsiveness to respiratory stimuli that resemble those of normal respiratory cells. In order to evaluate the possibility of experimental nerve banking, the feasibility of using short-term and long-term stored nerves as potential spinal nerve grafts was established using in vitro pre-degenerated nerve and cryopreserved nerve grafts after assessment of Schwann cell viability. The extent of respiratory reinnervation of the different grafts (medullary, spinal and stored nerve grafts) was compared. The discussion focuses on the main data and the strategy for future nerve grafting is evoked: functional characteristics of regenerating respiratory axons, extent of graft reinnervation, functional schwann cell survey within stored/grafted nerve and post-traumatic grafting.

Animals↗

PubMed2006

Neonatal lung and airway injury: a role for neurotrophins.

Maintenance of patency in distal airways is essential for gas exchange in neonatal life, and its disruption may have long-lasting effects on respiratory function. However, neural mechanisms that regulate caliber of intrapulmonary airways during early postnatal life, and their disruption by hyperoxic exposure, have not been well characterized. We have previously shown that cholinergically mediated airway contractile responses in rat pups are upregulated after hyperoxic exposure, and that increased expression of neuropeptides, such as substance P, may be contributory. More recently, we have documented impairment of neurally mediated airway relaxation in response to hyperoxic stress associated with loss of nitric oxide and prostaglandin-induced airway relaxation as well as inhibition of long chain myosin phosphatase. Our most recent data demonstrate significantly enhanced expression of the neurotrophin, brain-derived neurotrophic factor (BDNF) and its high affinity specific tyrosine kinase B (TrkB) receptor in hyperoxia-exposed airway smooth muscle. The existence of a BDNF-TrkB receptor autocrine and paracrine loops in the airways provides a basis for understanding local regulatory mechanisms of airway homeostasis. A mechanistic role for BDNF-TrkB signaling in hyperoxia-induced airway hyperreactivity in early postnatal life could serve to modulate both afferent and efferent neural pathways that result in enhanced contractile responses of immature airways exposed to hyperoxic stress. Greater insight into these neural pathways may lead to future preventive strategies for preterm infants surviving neonatal intensive care and developing chronic lung disease.

Animals↗