Biomedical subjects

J P Herman

Publications and source records attributed to J P Herman.

At least 91 records · Page 5Linked to original sources

PubMed1991

Long-term survival of intrastriatal dopaminergic grafts: modulation of acetylcholine release by graft-derived dopamine.

The nigrostriatal dopaminergic system of rats was unilaterally lesioned with 6-hydroxydopamine. Part of the animals was grafted 2 weeks later with fetal dopaminergic cells on the lesioned side; untreated rats of the same strain served as controls. Both 3 and 12-14 months after surgery the striatal dopamine (DA) content and the in vivo rotational response following injection of D-amphetamine showed significant changes in grafted as compared to lesioned animals. At 12-14 months after transplantation, the electrically evoked release of tritiated DA and acetylcholine (ACh) in slices (preincubated with [3H]DA or [3H]choline, respectively) of striata of intact, lesioned, or grafted animals was also investigated. Electrical field stimulation of striatal slices of the lesioned side did not evoke any significant [3H]DA overflow, whereas a marked [3H]DA release was observed in slices of grafted and control striata. Moreover, both DL-amphetamine (3 microM) and nomifensine (10 microM) strongly enhanced basal 3H outflow in these slices. Electrically evoked [3H]ACh release was significantly reduced in slices from all striatal tissues by 0.01 microM apomorphine. In slices from denervated striata a clearcut hypersensitivity for this action of apomorphine was present, indicating supersensitivity of DA receptors on cholinergic terminals; this hypersensitivity was significantly reduced in graft-bearing striata. Furthermore, because this hypersensitivity was unchanged in slices of lesioned striata under stimulation conditions (four pulses/100 Hz) avoiding inhibition by endogenously released DA, it is concluded that lesion-induced DA receptor supersensitivity is caused by an increase in receptor density or efficacy rather than by a decreased competition between endogenous and exogenous agonists. Both reuptake blockade of DA with nomifensine (10 microM) and release of endogenous DA by DL-amphetamine (3 microM) potently reduced [3H]ACh release only in control and grafted but not in lesioned tissue. In experiments using potassium-evoked [3H]ACh release, tetrodotoxin had no effect on the inhibitory activity of amphetamine and nomifensine, indicating that the DA receptors involved in their indirect inhibitory action are located directly on the cholinergic terminals.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1991

In situ hybridization analysis of arginine vasopressin gene transcription using intron-specific probes.

In situ hybridization histochemistry with a probe directed against an intron sequence of the rat arginine vasopressin (AVP) gene was used to demonstrate localization and regulation of AVP heteronuclear RNA in discrete brain regions. Hybridization with an AVP intron I (AVPinI) probe revealed specific hybridization confined to cell nuclei of paraventricular nucleus, supraoptic nucleus (SON), and suprachiasmatic nucleus neurons of the rat hypothalamus. Grain counts revealed that the signal generated by the AVPinI probe represented 1.9% of that derived from an AVP exon C probe (AVPexC) in the SON. Interestingly, in the suprachiasmatic nucleus the proportion of AVPinI to AVP exon C ratio was much higher (12%), suggesting either increased transcription of the AVP gene or changes in posttranscriptional RNA processing. Regulatory experiments revealed that 2.6-fold increases in AVPinI signal could be visualized in the SON as little as 30 min after an acute salt load, a period during which no significant change in cytoplasmic AVP mRNA could be observed. In response to chronic salt loading, both AVP heteronuclear RNA and AVP mRNA were up-regulated. These data compared favorably with transcription rate values determined by nuclear run-on assay, suggesting that intronic in situ hybridization affords a relatively reliable method for assessment of rapid changes in gene transcription in individual central nervous system neurons.

Animals↗

PubMed1990

Intra-accumbens implants of embryonic dopaminergic neurons reverse the behavioral supersensitivity to opiates evoked by lesion of the mesolimbic dopaminergic pathway.

The ascending mesotelencephalic dopaminergic systems of rat pups of 3 days of age were bilaterally lesioned using 6-hydroxydopamine injected at the level of the lateral hypothalamus. A sub-group of lesioned pups received, 5 days after the lesion, a dopamine neuron-rich cell suspension graft implanted bilaterally into the striatum and nucleus accumbens. Behavioral tests were conducted 6 months later. The lesion induced an increase in the locomotor activation induced by D-Ala2-Met5-enkephalinamide injected into the nucleus accumbens (2.5 micrograms/side) as compared to the activation observed in control animals. Locomotor activation by systemic apomorphine (0.1 mg/kg s.c.) was also increased while that induced by amphetamine (1.5 mg/kg i.p.) was abolished. The presence of DA neuron implants reversed each of these post-lesion modifications.

Amphetamine↗

PubMed1990

Importance of catecholamine release for the functional action of intrastriatal implants of adrenal medullary cells: pharmacological analysis and in vivo electrochemistry.

The aim of the present experiments was to test whether adrenal chromaffin cells implanted into the striatum of rats could exert a functional effect through a release of catecholamines. A cell suspension obtained from bovine adrenal medulla was implanted unilaterally into the striatum. The striatal dopaminergic input was extensively destroyed beforehand to preclude the possibility of reinnervation of the striatum by endogenous dopaminergic neurons. The functional influence of the implant was tested through the measurement of drug-induced rotation, while catecholamine release was measured subsequently in the same animals by in vivo electrochemistry. Transplant survival, as shown by the immunohistochemical analysis performed at the end of the in vivo experiments, was highly variable. Surviving chromaffin cells maintained their endocrine morphology and no reinnervation of the host striatum could be detected. Rotation of the animals evoked by apomorphine (0.1 mg/kg, sc) or amphetamine (5.0 mg/kg, ip) following the lesion was left uninfluenced following transplantation, even when a large transplant was recovered. On the other hand, nicotine (0.5 mg/kg, sc) evoked a strong contraversive rotational response in the transplant-bearing animals. This response could not be ascribed to the central effect of substances released peripherally and entering the nervous system through the blood-brain barrier opened by the implantation procedure, as it could not be found in animals bearing implants of other peripheral endocrine tissue, viz, pituitary. The effect of nicotine was not blocked by the pretreatment of the animals with either the opiate antagonist naloxone (2.5 mg/kg, 10 min) or the dopamine receptor blocker pimozide (0.5 mg/kg, 1 h), although the latter pretreatment blocked the amphetamine-evoked rotation. No spontaneous catecholamine release could be detected from the implanted chromaffin cells by in vivo electrochemistry, while treatment with amphetamine or nicotine did evoke a release. The results suggest that the functional effects of such intrastriatal grafts of chromaffin cells, reported in previous studies, cannot be explained by the secretion from the grafted cells of catecholamines into the denervated striatum. On the other hand the results obtained following the pharmacological stimulation of these cells indicate that adrenal grafts can, under suitable conditions, influence the functioning of the host nervous system.

Adrenal Medulla↗

PubMed1990

Behavioural effects of intracerebral dopaminergic grafts after neonatal destruction of the mesencephalic dopaminergic system.

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Animals↗

PubMed1990

Regulation of basal corticotropin-releasing hormone and arginine vasopressin messenger ribonucleic acid expression in the paraventricular nucleus: effects of selective hypothalamic deafferentations.

There exists considerable evidence to suggest that CRH and arginine vasopressin (AVP)-secreting parvocellular neurosecretory neurons of the hypothalamic paraventricular nucleus (PVN) are central integrators of negative feedback effects evoked by circulating glucocorticoid hormones. Most evidence suggests that these neurons may be receptive to circulating glucocorticoid levels, either via glucocorticoid receptors indigenous to these cells and/or via extrahypothalamic glucocorticoid-receptive neurons interacting with the PVN secretory cell. In an effort to address this issue, we performed anterior (ANT), posterior (POST) and total (TOT) deafferentations of the PVN region in male Sprague-Dawley rats using microknives fashioned from narrow-gauge spinal needles. Effective knife cuts were verified immunohistochemically, and deemed acceptable only if they avoided damage to the PVN proper and fibers of CRH and AVP-containing neurons coursing through the hypothalamus en route to the median eminence, while effectively eliminating neuronal input into the PVN region. Subsequent to surgery, levels of mRNA encoding for CRH and AVP in the parvocellular and magnocellular PVN were assayed via semiquantitative in situ hybridization histochemistry. Results indicate that TOT deafferentations resulted in significant increases in CRH mRNA expression in the PVN, and a slight but noticeable induction of AVP mRNA in the medial parvocellular but not posterior magnocellular divisions of the PVN. ANT lesions also produced an up-regulation of CRH and AVP mRNA relative to operated control rats. POST lesions did not produce a clear induction in either CRH or AVP mRNA. The data indicate that in the absence of neuronal input coming from anterior structures, CRH mRNA expression is up-regulated, suggesting that local effects of glucocorticoids on the PVN neuron are ineffective in maintaining normal CRH mRNA expression. These results support a role for neuronal feedback in regulation of the CRH neuron. The limited up-regulation (compared with adrenalectomized rats) of AVP mRNA in the TOT group suggests that while neuronal input may have some control of AVP mRNA expression, local glucocorticoid feedback is clearly able to restrict AVP message to levels considerably less than those seen in steroid-deficient animals. Analysis of knife-cut effects on plasma corticosterone and ACTH levels reveals that POST and TOT, but not ANT, deafferentations prohibit the secretory activity of the hypothalamo-pituitary-adrenocortical (HPA) axis seen pursuant to the anesthesia/thoracotomy in lesion and operated control groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗

PubMed1989

Chronic electroconvulsive shock treatment elicits up-regulation of CRF and AVP mRNA in select populations of neuroendocrine neurons.

The effects of repeated electroconvulsive seizures (ECS) on expression of mRNAs coding for corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) in neuroendocrine neurons of the hypothalamo-pituitary-adrenocortical (HPA) axis and hypothalamo-neurohypophysial system (HNS) were assessed via semi-quantitative in situ hybridization histochemical analysis. Measures of mRNA content were accompanied by measurement of peptide- and hormone-expression in the relevant neuroendocrine systems. Following 7 daily ECS treatments, CRF mRNA was significantly increased in the medial parvocellular paraventricular nucleus (PVN) of treated rats relative to controls. CRF peptide content of whole PVN homogenates was decreased to 50% of control levels. Changes in CRF message and peptide levels were accompanied by increases in pituitary ACTH content and by elevated plasma corticosterone, suggesting ECS elicits long-term up-regulation of the HPA axis. AVP mRNA in the medial parvocellular PVN, which is known to up-regulate in response to HPA challenge by adrenalectomy, was not increased by ECS. Chronic ECS causes a clear up-regulation of HNS neurons of the supraoptic nucleus, characterized by increased AVP mRNA content, decreased AVP peptide content, and depletion of neurohypophysial AVP. However, no changes were observed in magnocellular vasopressinergic neurons of the PVN, indicating that magnocellular SON and PVN neurons respond differentially to stimulation by ECS. The data indicate that ECS is a potent stimulus for activation of select components of both the HPA axis and the HNS. As such, ECS provides a useful tool for examining mechanisms underlying neuroendocrine processes.

Animals↗

PubMed1989

Localization and regulation of glucocorticoid and mineralocorticoid receptor messenger RNAs in the hippocampal formation of the rat.

Messenger RNAs coding for glucocorticoid (GR) and mineralocorticoid (MR) receptor proteins were localized to discrete subfields of the hippocampal formation by in situ hybridization histochemistry, using cRNA probes of approximately equivalent specific activity. Both GR and MR mRNAs were present in all subfields examined; GR mRNA was of greatest abundance in CA1, while MR mRNA was most densely labeled in CA3. In all subfields examined, MR mRNA was considerably more abundant than GR mRNA. Removal of circulating glucocorticoids by adrenalectomy precipitated an up-regulation of GR mRNA in subfields CA1-2 and the dentate gyrus, which was reversed by dexamethasone replacement. High doses of dexamethasone significantly down-regulated GR mRNA in CA3. In contrast, adrenalectomy produced significant up-regulation of MR mRNA only in subfield CA1-2. The data indicate that steroid receptor mRNAs are differentially distributed in hippocampus, and that sensitivity to steroids occurs within defined structural domains of the hippocampal formation.

Adrenalectomy↗

PubMed1989

Evidence for hippocampal regulation of neuroendocrine neurons of the hypothalamo-pituitary-adrenocortical axis.

Expression of mRNAs coding for the ACTH secretagogues corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) was examined in the hypothalamic paraventricular nucleus (PVN) of rats bearing hippocampal lesions. Either total hippocampectomy (HPX) or extirpation of the dorsal hippocampus (DHPX) precipitated a 4-fold increase in CRF mRNA expression relative to sham-operated controls (SHAM), as determined by semiquantitative in situ hybridization histochemistry. AVP mRNA was localized to individual parvocellular neurons of the medial parvocellular division of the PVN in only the HPX and DHPX groups, consistent with enhanced production of AVP message in this neuronal population subsequent to hippocampal damage. HPX did not affect AVP mRNA content in magnocellular divisions of PVN. Plasma beta-endorphin levels were significantly elevated in the HPX and DHPX groups relative to SHAM animals, indicating a chronic increase in release of proopiomelanocortin peptides from the anterior pituitary gland in response to hippocampal lesion. Circulating corticosterone levels were elevated in HPX rats as well. To control for effects of lesion size and location, additional animals received large ablations of cerebral cortex or cerebellum. In neither case was CRF or AVP mRNA significantly altered in the PVN. The results suggest that the hippocampus exercises a tonic inhibitory role on ACTH secretagogue production in neuroendocrine neurons promoting ACTH release.

Animals↗

PubMed1988

Intracerebral dopaminergic transplants are not activated by electrical footshock stress activating in situ mesocorticolimbic neurons.

Male rats received a dopaminergic implant aimed either at the nucleus accumbens or the ventral tegmental area (VTA) following 6-hydroxydopamine lesion of their mesocorticolimbic dopaminergic system. Exposure to electrical footshock stress 6 months later markedly activated the mesocorticolimbic neurons in control animals as shown by the increase of dihydroxyphenylacetic acid (DOPAC) levels both in the nucleus accumbens and the VTA. However, no stress-induced activation was seen for the grafted neurons, irrespective of the area of implantation. These results indicate the lack of reinnervation and modulation of the grafted dopaminergic neurons by one of the important afferent systems regulating the activity of endogenous mesencephalic dopaminergic neurons.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1988

Development of intracerebral dopaminergic grafts: a combined immunohistochemical and autoradiographic study of its time course and environmental influences.

The aim of the study was to obtain a description of some aspects of the development of intracerebral dopaminergic grafts, namely, the time course of the glial reaction and its relation to cell division on one hand, and the development of graft-originated innervation and its dependence on adequate matching of the implanted neurons and target site on the other hand. Cell suspensions obtained from the mesencephalon or hypothalamus of embryonic day (ED) 14 rat embryos were implanted into the striatum or lateral hypothalamus of adult rats following the destruction of the nigrostriatal system of the hosts. Animals were sacrificed at different postimplantation times, and the development of the graft was followed by immunohistochemistry by using antisera directed against tyrosine hydroxylase (TH) or glial fibrillary acidic protein (GFA). Furthermore, the existence of cell division at various times following implantation was examined by performing autoradiography on immunostained sections after prior intraventricular administration of 3H-thymidine to the host. The first stage of the development of intracerebral grafts was characterized by the existence of intense cell division within the grafted tissue, lasting about 2 weeks, and also in the host tissue surrounding the graft, lasting only about 6 days. The cell division in the host tissue was paralleled by the existence of a strong glial reaction which, however, did not extend into the graft itself. Glial reaction in the host tissue gradually decreased at later times and disappeared by 4 weeks postimplantation without leaving behind a noticeable glial scar. The graft itself was, however, transiently filled with a population of reactive astroglial cells between 3 and 6 weeks postimplantation. Within grafts of mesencephalic tissue located in the striatum TH-positive neurons were distributed evenly at short times postimplantation (2-6 days). At later time a compartmentation could be observed, with TH-positive neurons being aligned along the graft-host interface or clustered within the graft itself. Innervation of the host tissue by TH-positive fibers increased between 1 and 6 weeks postimplantation. On the other hand, no compartmentation and reinnervation of surrounding host tissue was observed for intrahypothalamic grafts of mesencephalic tissue or intrastriatal grafts of hypothalamic tissue. This last observation indicates that adequate matching of implanted neurons and target tissue plays an important role in the development of intracerebral dopaminergic grafts.

Animals↗

PubMed1988

Distorted development of intracerebral grafts: long-term maintenance of tyrosine hydroxylase-containing neurons in grafts of cortical tissue.

Cortical cells obtained from rat embryos (ED14 to ED20) were implanted in various regions of rat brain and the presence of tyrosine hydroxylase (TH)-, neuropeptide Y (NPY)- and Met-enkephalin (ENK)-immunoreactive neurons within the grafts were tested using an immunohistochemical approach. TH-like immunoreactive (TH-LI) neurons were present within the implants obtained from ED14, but not ED18 or ED20, embryos up to 10 months post-implantation and their presence was not dependent on the age of the host (adult or neonate) at the time of implantation. Furthermore, the density of such cells varied with the site of implantation, being the highest in the dorsomedial corner of the striatum. This distorted development seems to affect also other cell populations, such as NPY-LI neurons which could be observed within the implants in a density much higher than that found in the normal cortex and which presented generally a rather immature morphology. It has been described that the rat cortex contains TH-LI neurons only during a limited period of development. The survival of such neurons within intracerebral grafts of cortical tissue indicates that their disappearance during normal cortical development is dependent upon environmental cues. The survival of TH-LI cells in grafts implanted to neonatal hosts suggests that these cues are not some humoral factors appearing postnatally. On the other hand, the present observations are compatible with several other hypothesis concerning the nature of such cues: humoral factors present during the late embryonic period, signals dependent on neuronal connectivities (input and/or outputs) established during embryonic or postnatal life.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1988

Intrastriatal dopaminergic grafts restore inhibitory control over striatal cholinergic neurons.

The aim of the study was to examine the influence of intrastriatal dopaminergic grafts on the functioning of striatal cholinergic neurons using an in vitro superfusion method. Rats bearing unilateral 6-hydroxydopamine lesion of the nigrostriatal dopaminergic system received a cell suspension obtained from ED 14 rat embryonic mesencephali which was injected into the denervated striatum. Lesioned animals displayed an ipsilateral rotation in response to amphetamine (5 mg/kg i.p.). This rotational response disappeared following grafting and there was even a significant contralateral rotation in response to the drug. Apomorphine (0.1 mg/kg s.c.) induced a contralateral rotation following the lesion. This latter response was attenuated in the grafted group. Three months after grafting 350 microns thick slices were prepared from striata from the control and experimental sides of lesioned and graft-bearing animals. The slices were preincubated either with 3H-dopamine (10(-7) M) or 3H-choline (10(-7) M) and then superfused with an oxygenated Krebs-Ringer solution. Stimulation with electrical pulses following preincubation with 3H-dopamine elicited a marked increase of tritium outflow from control slices. Stimulation-evoked overflow was of similar magnitude from slices from striata containing the graft, while it was much reduced in slices from lesioned striata. Amphetamine markedly potentiated the effect of electrical stimulation in slices obtained from control and graft-containing striata. Nomifensine (a dopamine uptake blocker) led to a significant decrease of the overflow of 3H-acetylcholine evoked by electrical stimulation from control striatal slices. This inhibition was antagonized by domperidone, a D2 dopamine receptor blocker, a finding which indicates that the action of nomifensine was indeed due to a potentiation of the action of endogenous dopamine released by the electrical stimulation. A similar, although somewhat attenuated, action of nomifensine and domperidone was observed for striatal slices containing the graft. Amphetamine inhibited the stimulation evoked overflow of 3H-acetylcholine in a dose-dependent manner from striatal slices obtained both from the intact and experimental sides of graft-bearing animals, while it had no action on slices from denervated striata. Finally, the dose-response curve for the inhibition of 3H-acetylcholine release by apomorphine was significantly shifted to the left for slices from the lesioned striata as compared with control slices. This leftward shift was totally abolished in the slices from the graft-containing striatum.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗

PubMed1988

Effects of intra-accumbens dopaminergic grafts on behavioral deficits induced by 6-OHDA lesions of the nucleus accumbens or A10 dopaminergic neurons: a comparison.

Local lesion of the dopaminergic (DA) terminals of the nucleus accumbens have been described to reproduce part of the behavioral deficits evoked by the lesion of the whole mesocorticolimbic DA system. The most straightforward interpretation of these results would be that the DA innervation of the nucleus accumbens is necessary for and critically involved in the normal performance of the given behaviors. However, while giving some indication as to the necessity of the integrity of this DA innervation for normal behaviors, such an approach cannot reveal whether the presence of the DA innervation of other mesocorticolimbic areas (e.g. amygdala, septum, etc.) is also required. In order to approach this question, the behavioral effects of DA grafts implanted into the nucleus accumbens of rats were evaluated following two different 6-hydroxydopamine-induced lesions: a lesion restricted to the anterior DA field (DA terminals of the nucleus accumbens and to a lesser degree the frontal cortex and anteromedial striatum) or a lesion of the whole mesocorticolimbic DA system. The latter lesion induces a disappearance of the DA innervation of the nucleus accumbens as well as the amygdala, septum, etc. Both kinds of lesions led to locomotor hypoactivity, loss of locomotor activation by amphetamine, increased locomotor stimulation to apomorphine, decrease of exploratory activity and loss of hoarding behavior. These deficits were not seen in grafted animals bearing a local lesion of the DA innervation of this structure. For some of these recoveries, however, a pharmacological stimulation of the grafted neurons was required to reveal the effect of the graft. In the case of the total lesion of the mesocorticolimbic DA system, only locomotor dysfunctions were compensated by the intra-accumbens DA implants, while the other deficits remained intact, irrespective of a stimulation of the graft. These results indicate that the re-establishment of the DA innervation of the nucleus accumbens is a sufficient condition for the compensation of locomotor deficits, irrespective of the presence of the DA terminals in more posterior limbic structures, while for deficits of more complex behaviors the simultaneous presence of posterior DA innervations is also required. This latter requirement suggests the existence of some cooperativity between the different central DA terminal areas for the normal performance of behaviors.

Animals↗

PubMed1988

[Immunocytochemical study of catecholaminergic neurons in grafted mesencephalon transplanted into the hypothalamus of the rat].

Mesencephalic fragments from 14 day old embryonic rat brain were transplanted into the third ventricle of adult rats neonatally treated with monosodium glutamate. From two to twelve months after grafting, the implanted tissue was still present in the ventricle and contained TH immunoreactive neurons which displayed a normal appearance at ultrastructural level. While endogenous TH containing neurons were still present in dopaminergic regions of the recipient hypothalamus, grafted mesencephalic fragments could survive and develop. They contained TH immunopositive most probably dopaminergic neurons which are able, in some cases, to innervate the host brain. This model should be of interest in the study of neuroendocrine functions of dopaminergic neurons.

Animals↗

PubMed1988

Differentiation of corneal complications observed in contact lens wearers.

Corneal epithelial cystic formations and epithelial infiltrates are relatively common in contact lens patients. Accurate diagnosis of these conditions is needed for proper management of the patient, but the observation and differential diagnosis is hampered by the minute size and similar biomicroscopic appearance of these conditions. This paper presents a description of these subtle formations and the slit lamp techniques for differentiating epithelial microcysts, vacuoles, bullae, and infiltrates. The clinical significance of these conditions is also discussed.

Contact Lenses↗

PubMed1987

Spontaneous and graft-induced behavioral recovery after 6-hydroxydopamine lesion of the nucleus accumbens in the rat.

In the present study the long-term evolution of behavioral deficits following a local lesion of the dopaminergic innervation of the nucleus accumbens with 6-hydroxydopamine (6-OHDA) was compared in two groups of rats: lesioned animals and animals bearing a dopaminergic implant in the nucleus accumbens. Lesioned animals gradually recovered on various behavioral tests (amphetamine-induced locomotion, exploration, hoarding) and were indistinguishable from the control group on most parameters by 10 months postlesion. The deficits were, however, reinstated by a second intra-accumbens 6-OHDA lesion, a finding which suggests a role for dopaminergic reinnervation in the observed recovery. Conversely, grafted animals still displayed marked deficits even 10 months after grafting, although the lesioned areas were well reinnervated by the graft. These results indicate that the graft, while being unable on its own to compensate for part of the deficits, can nevertheless impair and compete with endogenous processes leading to behavioral recovery following a local lesion.

Animals↗