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Generation of rapid eye movements during paradoxical sleep in humans.

Although rapid eye movements (REMs) are a prominent feature of paradoxical sleep (PS), their origin and functional significance remain poorly understood in humans. In animals, including nonhuman primates, REMs during PS are closely related to the occurrence of the so-called PGO waves, i.e., prominent phasic activities recorded throughout the brain but predominantly and most easily in the pons (P), the lateral geniculate bodies (G), and the occipital cortex (O). Therefore, and because the evolution of species is parsimonious, a plausible hypothesis would be that during PS in humans, REMs are generated by mechanisms similar to PGO waves. Using positron emission tomography and iterative cerebral blood flow measurements by H(2)(15)O infusions, we predicted that the brain regions where the PGO waves are the most easily recorded in animals would be differentially more active in PS than in wakefulness, in relation with the density of the REM production [i.e., we looked for the condition (PS versus wakefulness) by performance (REM density) interaction]. Accordingly, we found a significant interaction effect in the right geniculate body and in the primary occipital cortex. The result supports the hypothesis of the existence of processes similar to PGO waves in humans, responsible for REM generation. The interest in the presence of PGO waves in humans is outstanding because the cellular processes involved in, or triggered by, PGO waves might favor brain plasticity during PS.

Adult↗

[Evaluation of electrophysiological neuromonitoring in the diagnosis of brain death: Part I. Brainstem auditory evoked potentials].

Electrophysiological neuromonitoring of brainstem auditory evoked potentials (BAEP), short-latency somatosensory evoked potentials (SSEP) and compressed spectral array (CSA) EEG can provide precise and immediate information concerning functional integrity of the brain, brainstem and upper spinal cord of severely brain-damaged patients. We applied this neuromonitoring system in the cases of 154 severely brain-damaged patients in order to evaluate its reliability in the diagnosis of brain death. In particular, this study considers the relationships between BAEP and neurological findings, conventional EEG findings and factors affecting final BAEP findings. As a result, we evaluated the significance of BAEP in the diagnosis of brain death. A total of 109 brain-dead patients were divided into two groups: group A with 48 patients determined brain dead neurologically and by EEG prior to BAEP monitoring, and group B with 61 patients who had undergone automatic BAEP monitoring every 10 to 30 minutes before and/or after determination of clinical brain death. A third group, C, included 45 non brain-dead patients subjected to neuromonitoring, and served as a comparative group. Brain damage was caused by subarachnoid hemorrhage in 50 patients, intracerebral hemorrhage in 36, cerebral infarction in 8, head injury in 47, meningitis in 3, brain tumor in 3 and anoxia in 7. There were no significant differences in causes among the three groups (chi 2 = 20.3). The mean ages in the three groups were 50 (ages 10-91) in group A, 51 (14-86) in group B, and 50 (5-87) in group C. There were no significant differences in age distribution among the three group (chi = 25.0). The last BAEP findings of the 109 brain-dead patients indicated loss of all waves in 99 (91%), the presence of wave I in 9 (8%), and the presence of waves I and II in one patient (1%) (Table 1). Only three of the 45 group C non brain-dead patients indicated loss of all BAEP waves within one month after onset (Table 1). The one demonstrated loss of all BAEP waves 17 days after her accident, with recovery of waves I to V three months later. The temporal relationships in group B patients of the course of BAEP findings and the time of neurological brain death diagnosis are shown in Table 2 and Fig. 1. All but two of the 61 patients were followed up until final loss of BAEP waves (Fig. 1).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Spinal evoked potentials following transcranial magnetic stimulation.

Motor evoked potentials by magnetic stimulation is less invasive and causes no pain as opposed to high current electric stimulation. However, the distribution of the magnetic field generated by the round coil has not been fully studied. In this report, we mapped the extent of the magnetic induction flux density, and then the evoked potentials from the spinal cord were investigated by transcranial magnetic stimulation. We also examined the origin of the evoked potentials obtained by the magnetic stimulation. The following results were obtained. The magnetic induction flux density was at its maximum at the edge of the coil. The potentials consisted of a first negative wave and subsequent multiphasic waves. The first negative wave was similar to a response of the subcorticospinal tract in the lower brain stem, while the subsequent multiphasic waves were similar to those of the pyramidal tract. Although magnetic stimulation has certain advantages over electric stimulation, several problems remain to be solved for the monitoring of motor functions in the clinical settings.

Animals↗

Military TBI during the Iraq and Afghanistan wars.

Traumatic brain injury (TBI) is an important source of morbidity in the Iraq and Afghanistan wars. Although penetrating brain injuries are more readily identified, closed brain injuries occur more commonly. Explosion or blast injury is the most common cause of war injuries. The contribution of the primary blast wave (primary blast injury) in brain injury is an area of active research. Lessons learned from the sports concussion and civilian mild TBI literature are useful. Individuals with TBI and posttraumatic stress disorder require treatment of both conditions. Families and communities need to be cognizant of the needs of these returning veterans.

Afghanistan↗

[Auditory evoked brain-stem responses (ABRs) in brain dead status].

Auditory evoked brain-stem responses (ABRs) were recorded in 19 out of 52 brain dead cases in Department of Emergency Medicine, University of Tokyo Hospital from May, 1981 to January, 1984. The causes of brain death were severe head injury (9 cases), cerebro-vascular disease (7 cases), anoxia (2 cases), hydrocephalus (1 case). Eleven cases of them fulfilled the clinical criteria which included absence of cortical and brain-stem functions excluding severe hypothermia and depressant drug intoxication. The remainders who were subjected to barbiturate therapy were diagnosed as brain death for non-filling phenomenon in cerebral angiography. Results were as follows; Fourteen cases (74%) had no identifiable ABR waves. One case (5%) had only 1st wave. Three cases (16%) had 1st and 2nd waves. One case (5%) had 1st, 2nd, and 3rd waves. In spite of definition of clinical brain death, 5 cases had at least 1st wave, and therefore these datum suggested that ABR might have less clinical utility in diagnosis of brain death. Each case did not necessarily demonstrate the total extinction of ABRs, as was shown in (2) to (4) mentioned above. The clinical status which met the criteria of brain death might therefore possibly imply any conditions in which brain death was impending gradually to result in the total brain death of cerebrum through medulla oblongata. Under these circumstances, how barbiturate might produce ABRs abnormality remained unsolved, though it has been said not to produce ABRs abnormality. Among 8 cases under barbiturate therapy, there were 5 cases with no identifiable waves and 3 cases with 1st and 2 nd waves.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Interactions of age, gender, and sensorineural hearing loss on ABR latency.

The interactive effects of gender, age, and degree of sensorineural hearing loss on the absolute latency of wave V of the auditory brain stem response were analyzed in 325 subjects with cochlear loss. Norms based on these data were then applied to an analysis of the wave V latencies of 87 subjects with retrocochlear loss. Results in the cochlear group revealed interactions between gender and age and between gender and degree of hearing loss. The interactive effect between gender and degree of loss was observed for wave V, but not for waves III or I. Separate gender norms for absolute wave V latency, based on empirical boundaries encompassing 99% of the cochlear group, resulted in a 90% correct identification rate in the 87 subjects with retrocochlear lesion.

Adolescent↗

Kappa opiate receptor agonists: effects on behavior and on brain function and structure in rhesus monkeys.

In the present study several drugs that are predominantly agonists of kappa receptors were tested in rhesus monkeys prepared with deep and surface brain electrodes. The administration of two benzomorphan derivatives and of ethylketocyclazocine induced acute behavioral effects resembling catatonia concomitant with generalized spike and slow-wave electroencephalographic activity at widespread brain sites, that lasted for about 1 hr. After administration of one to three doses of these agonists (the benzomorphan derivatives to five monkeys and the ethylketocyclazocine to two monkeys), chronic recording changes developed, characterized by continuous high-amplitude spiking activity focal at the anterior septal region and periaqueductal gray of the mesencephalon. They increased in intensity with the passage of time, the monkeys having been followed as long as 5 months without further drug administration. Light microscopy and electron microscopy showed no structural abnormalities in the monkey brains at the sites of altered recordings, although occasional dendritic atrophy was noted at all cortical and subcortical brain sites examined. Chronic recording changes did not develop in a monkey that received U-50,488H on eight occasions. And none of the electrode-implanted monkeys that served as controls (having received no kappa agonists) developed recording changes. The sites affected by the active kappa agonists were those at which abnormal activity has been correlated with psychotic behavior. The ability of the kappa agonists to induce a lasting physiologic change without corresponding structural change at those focal sites implicated in schizophrenia may prove a useful probe in further investigations into the cause of schizophrenia and its ultimate treatment.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Bilateral recording of early auditory evoked responses in the cat.

The brain-stem electric responses of the cat evoked by a short 4 kHz tone burst have been differentially recorded between vertex and both ipsilateral and contralateral ear electrodes. Six vertex-positive waves can be recognised in both recordings. Animals with hereditary unilateral anacusis were studied in order to avoid cross-stimulation of the opposite ear. The cochlear microphonic and summating potential can be readily recorded in young animals, occur simultaneously in both tracings, and show polarity inversion at the contralateral electrode. The later neural potentials have the same polarity and practically identical latencies in the ipsilateral and contralateral recordings, whilst the first three brain-stem waves show approximate polarity inversion and variable latency relationships in the two recording situations. It is concluded that none of the brain-stem waves represents electric activity from a discrete generator.

Animals↗

The cellular basis of neurovascular metabolic coupling.

Functional brain imaging studies, such as positron emission tomography and functional nuclear magnetic resonance imaging, are based on the regional increases in cerebral blood flow, glucose consumption and oxygen consumption that are associated with regional increases in neuronal activity. The cellular basis of the signals that are measured is however incompletely understood at present. An increasingly important role for astrocytes in neurovascular metabolic coupling is being described, which was already suggested over 100 years ago as astrocytes are a structural link between endothelial cells of brain capillaries and neurons. Recent data have provided evidence for a role of the astrocytic intracellular sodium concentration in driving astrocytic glycolysis that may provide neurons with lactate as an energy substrate during activation. We have previously described intracellular sodium changes in astrocytes that are associated with astrocytic intercellular calcium waves. These intercellular calcium waves have been demonstrated both in astrocytes in culture as well as in brain slices. In this paper a new hypothesis concerning a role for astrocytic intercellular calcium waves in brain energy metabolism is formulated.

Animals↗

Interstitial white matter brain oedema does not alter the electroencephalogram.

An experimental study was performed to determine the effects of interstitial white mater oedema on the electroencephalogram (EEG). Using both rodent and feline infusion models of focal brain oedema no difference was found between the EEG waveforms recorded epidurally from the infused and control hemispheres. It is concluded that where focal slow-wave EEG abnormalities overlie oedematous brain the EEG abnormalities are not primarily related to the brain oedema but arise from either local biomechanical or other pathophysiological mechanisms.

Animals↗

Clinical and pathologic characteristics of nontyphoidal salmonella encephalopathy.

OBJECTIVE: To investigate the clinical and pathologic characteristics of primary encephalopathy caused by nontyphoidal salmonellosis (NTS). METHODS: Case records of six Japanese hospitals from 1994 to 1999 were reviewed. Eight cases of primary NTS encephalopathy were identified based on strictly defined criteria: 1) encephalopathic feature defined as altered state of consciousness, altered cognition or personality, or seizures; 2) detection of nontyphoidal Salmonella species in stool; 3) absence of other viral or bacterial infection associated with CNS abnormalities; and 4) absence of alternative explanation by underlying neurologic or systemic disease. Three patients died, three had severe sequelae, and two recovered completely. The authors analyzed their clinical course, neurologic symptoms, and histopathologic findings. RESULTS: NTS encephalopathy was clinically characterized by diffuse and rapidly progressive brain dysfunction and circulatory failure that developed following enteritis. There was no evidence of severe dehydration or sepsis, and encephalopathy was rarely accompanied by abnormal laboratory data, except elevated CSF opening pressure, brain edema on CT, and slow waves on EEG. Pathologic findings included minimal ischemic damage and mild edema in the brain, microvesicular fatty change of the liver, severe enterocolitis but no evidence of dehydration, and no fatal organ damage including microvasculature and endothelial cells. CONCLUSION: Noninfectious encephalopathy associated with nontyphoidal salmonella infection is a distinctive clinical entity that can be differentiated from Reye's syndrome and Ekiri.

Adolescent↗

The gamma-hydroxybutyrate model of absence seizures: correlation of regional brain levels of gamma-hydroxybutyric acid and gamma-butyrolactone with spike wave discharges.

gamma-Hydroxybutyric acid (GHB) produces a constellation of EEG and behavioral changes when given to animals, which represent an experimental model of generalized absence seizures. gamma-Butyrolactone (GBL), the prodrug of GHB, produces these changes more rapidly and consistently than GHB, such that the rat treated with GBL is a more reproducible and predictable model of absence seizures. The hypothesis that the epileptogenic effects of GBL are due solely to its conversion to GHB was tested. The regional concentration of both compounds in brain was determined in time-course and dose-response studies, as well as at the onset of EEG changes, induced by both GHB and GBL. Also, the EEG and behavioral effects of both drugs were ascertained after intrathalamic injection in the rat. gamma-Butyrolactone produced a rapid onset of bilaterally synchronous spike and wave discharges in the rat, which correlated with a rapid appearance of GHB in brain in the GBL-treated animals. In the GHB-treated animals, EEG changes occurred 20 min after administration of GHB when levels of GHB in the brain were peaking. The threshold concentration of GHB in brain for EEG changes, in both GHB-and GBL-treated animals was 240 x 10(-6) M. The concentration of GBL in brain peaked 1 min after administration of GBL and fell rapidly to undetectable levels within 5 min. Bilateral injection of GHB into thalamus resulted in a brief burst of spike and wave discharges, while GBL, administered into the thalamus, had no effect. The use of GBL as a prodrug for GHB in this model of generalized absence seizures is valid, since GBL itself was inactive.

4-Butyrolactone↗

Effect of the oral administration of branched chain amino acids on hepatic encephalopathy in the rat.

The aim of this study was to investigate the effect of oral administration of branched-chain amino acid (BCAA)-enriched diets after portacaval shunt (PCS) in rats. Fifty-one Sprague-Dawley male rats (200 gm) underwent PCS and 55 a sham operation. Half of the animals received BCAA 142 mg per day through a gastric tube; the other half underwent a sham procedure. Sleep disturbances were evaluated at 7, 14, and 28 days postoperatively by measurement of the excitability of the reticular brain-stem formation during the slow-wave sleep and paradoxical sleep. Animals were killed at the same intervals and liver/body weight ratio, plasma, and brain amino acids, brain norepinephrine, brain serotonin, 5-hydroxyindolacetic acid and histamine were measured. Each group of animals was matched with a similar group of sham-operated rats, i.e., receiving or not receiving BCAA. After PCS (as compared to sham-operated animals) a significant hyperexcitability of the reticular brain-stem formation was found during the slow-wave sleep. The liver/body weight ratio was significantly lower. Tryptophan (free tryptophan in the plasma), phenylalanine, tyrosine, and histidine increased in the plasma and the brain. Leucine and isoleucine were decreased in the plasma. After PCS, an initial decrease at 7 days postoperatively of brain norepinephrine and blockade of the intracerebral metabolism of tryptophan were observed. These changes were transient and progressively disappeared at 14 and 28 days postoperatively. Brain histamine remained at a very high level through the experiment. A good correlation was demonstrated between modification of the sleep disturbance and tryptophan (or 5- hydroxyindolacetic acid) and histamine brain levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

The relationship between cerebral blood flow velocity fluctuations and sleep state in normal newborns.

Cerebral blood flow velocity was recorded for an average of 23 4-min epochs during natural sleep in 11 normal full-term newborn babies. Intracranial pressure, core temperature, and respiration were simultaneously and non-invasively monitored. Sleep state was classified using information from EEG, pattern of respiration, and eye and body movements by a trained observer. From a total of 238 epochs, 66 were considered to occur in quiet sleep, 101 in active sleep, and in 77 the baby was awake, in a transitional state or moving excessively. Slow cyclical variations in cerebral blood flow velocity were observed with a frequency of between 2 and 6 cycles/min, and these were of significantly greater amplitude during quiet sleep (24%) compared to active sleep (16%; p < 0.0001, Mann Whitney U test). There was no difference in median cerebral blood flow velocity (7.5 cm/s). The cyclical variation observed in normal babies were similar to those described in preterm babies and adults, at a similar frequency to B waves in intracranial pressure. They may represent vasomotor waves in the small autoregulatory arteries of the brain. Reduction in sensitivity of the receptors initiating the waves may occur in active sleep or there may be competition from other oscillatory mechanisms.

Blood Flow Velocity↗

Development of shock wave assisted therapeutic devices and establishment of shock wave therapy.

In order to exploit systems for shock wave therapy, we are working for the development of clinical devices that are based on the concept of shock waves or related phenomena. The paper describes these new therapeutic devices designed for the minimally invasive approach to vascular thromboloysis, selective dissection of tissues, and drug or DNA delivery. To investigate the response of cells to shock loading, a precise method of shock waves generation in space and time has been developed. This method has been studied for application in cardiovascular therapy, cancer treatment, and cranioplasty in close vicinity of the brain. A laser ablation shock wave assisted particle acceleration device has been developed for delivering drug and DNA into soft targets in the human body. The penetration depth of microparticles observed in the experimental targets is believed to be sufficient for pharmacological treatments. In order to achieve an efficient method for rapid revascularization of cerebral thrombosis, a laser induced liquid jet (LILJ) system has been developed. The LILJ has been successfully applied for selective dissection of soft tissue preserving nerve and blood vessels. The system has been further improved by using piezoelectric actuators to drive the liquid jets, as an alternative to pulse laser.

Animals↗

Mild hypoglycemia and impairment of brain stem and cortical evoked potentials in healthy subjects.

To evaluate the impact of mild hypoglycemia on CNS function in healthy adults, we measured brain stem auditory evoked potentials and P300 potentials (elicited by cognitive processing of auditory stimuli) during hypoglycemic or euglycemic insulin clamps (80 mU.m-2.min-1). In the hypoglycemic clamp study (n = 8), plasma glucose was allowed to fall from 4.6 to 3 mM in hourly approximately 0.5-mM steps and subsequently returned to euglycemic baseline levels. In the euglycemic clamp study (n = 8), plasma glucose was maintained at baseline levels throughout. Neither brain stem nor P300 responses changed during the euglycemic control study; symptoms and counterregulatory hormones were also unaffected. During the hypoglycemia study, epinephrine and growth hormone rose once plasma glucose reached 3.4 +/- 0.1 mM. Brain stem and P300 potentials remained unchanged until the 3-mM glucose step, when neurophysiological changes suddenly developed in conjunction with reported symptoms. At this glucose level, the wave V component of the brain stem potential was selectively altered in 7 of 8 subjects. Furthermore, P300 latency significantly increased, and amplitude diminished. Changes in both brain stem and cortical (P300) responses reversed when euglycemia was restored. We conclude that modest reductions in plasma glucose (to 3 mM) produce marked alterations in both brain stem and cortical responses to auditory stimuli. These changes in neural function appear at the same time as symptoms and follow rather than precede the rise in counterregulatory hormones during hypoglycemia. Our data suggest that the adverse effects of mild hypoglycemia on brain function are not limited to higher centers but also involve the brain stem.

Adult↗