Environmental enrichment reduces brain excitability in adult rats overnourished during lactation / Enriquecimento ambiental reduz excitabilidade cerebral em ratos adultos hipernutridos durante a lactação

ABSTRACT Objective: This study aimed to analyze whether exposure to environmental enrichment (EE) during the juvenile phase of life interferes with the electrical activity of the adult rat brain. In addition, the present research also investigated whether this putative effect on brain electrical activity could be affected by prior overnutrition during lactation. Electrophysiology was measured through cortical spreading depression (CSD), a phenomenon related to brain excitability. Methods: Wistar rats were suckled in litters of either nine or three pups, forming the nourished (N) or overnourished (ON) groups, respectively. At 36 days old, half of the animals from each nutritional condition were exposed to EE. The other half was kept in the standard environment (SE). At 90-120 days of life, each animal was anesthetized for CSD recordings. Results: Overnutrition during lactation caused increases (p < 0.05) in body and brain weights. The EE decelerated CSD propagation velocity regardless of nutritional state during lactation (p < 0.001). The CSD deceleration in the N-EE group was 23.8% and in the ON-EE group was 15% in comparison with the N-SE and ON-SE groups, respectively. Conclusion: Our data demonstrated that EE exposure in the juvenile phase of the rat's life reduced brain excitability, and this effect was observed even if animals were overnourished during lactation. An EE could be considered an adjuvant therapeutic resource to modulate brain excitability.

RESUMO Objetivo: Este estudo analisou se a exposição ao ambiente enriquecido durante a fase juvenil da vida interferiria na atividade elétrica do cérebro de ratos adultos. Além disso, a presente pesquisa também investigou se esse provável efeito na atividade elétrica cerebral poderia ser afetado pela hipernutrição durante a lactação. A eletrofisiologia foi medida através da depressão alastrante cortical, um fenômeno relacionado à excitabilidade cerebral. Métodos: Ratos Wistar foram amamentados em ninhadas de nove ou três filhotes, formando os grupos nutridos ou hipernutridos, respectivamente. Aos 36 dias, metade dos animais de cada condição nutricional foram expostos ao ambiente enriquecido. A outra metade foi mantida na condição de ambiente padrão. Aos 90-120 dias de vida, foram obtidos os registros da depressão alastrante cortical. Resultados: A hipernutrição durante a lactação causou incrementos (p < 0,05) nos pesos corporal e cerebral.O Ambiente Enriquecido desacelerou a velocidade de propagação da depressão alastrante cortical independentemente do estado nutricional durante a lactação (p < 0,001). A desaceleração da depressão alastrante cortical no grupo nutrido/ambiente enriquecido foi de 23,8% e no grupo hipernutrido/ambiente enriquecido foi de 15% em comparação com os grupos nutrido/ambiente padrão e hipernutrido/ambiente padrão, respectivamente. Conclusão: Nossos dados demonstram que a exposição ao ambiente enriquecido na fase juvenil da vida do rato reduz a excitabilidade cerebral, e esse efeito pode ser observado mesmo se os animais estiverem hipernutridos durante a lactação. O ambiente enriquecido pode ser considerado um recurso terapêutico adjuvante para modular a excitabilidade cerebral.

History of Migraine and Volume of Brain Infarcts: The Italian Project on Stroke at Young Age (IPSYS) / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Migraine has been shown to increase cerebral excitability, promote rapid infarct expansion into tissue with perfusion deficits, and result in larger infarcts in animal models of focal cerebral ischemia. Whether these effects occur in humans has never been properly investigated. METHODS: In a series of consecutive patients with acute ischemic stroke, enrolled in the setting of the Italian Project on Stroke at Young Age, we assessed acute as well as chronic infarct volumes by volumetric magnetic resonance imaging, and compared these among different subgroups identified by migraine status. RESULTS: A cohort of 591 patients (male, 53.8%; mean age, 37.5±6.4 years) qualified for the analysis. Migraineurs had larger acute infarcts than non-migraineurs (median, 5.9 cm³ [interquartile range (IQR), 1.4 to 15.5] vs. 2.6 cm³ [IQR, 0.8 to 10.1], P<0.001), and the largest volumes were observed in patients with migraine with aura (median, 9.0 cm³ [IQR, 3.4 to 16.6]). In a linear regression model, migraine was an independent predictor of increased log (acute infarct volumes) (median ratio [MR], 1.64; 95% confidence interval [CI], 1.22 to 2.20), an effect that was more prominent for migraine with aura (MR, 2.92; 95% CI, 1.88 to 4.54). CONCLUSIONS: These findings reinforce the experimental observation of larger acute cerebral infarcts in migraineurs, extend animal data to human disease, and support the hypothesis of increased vulnerability to ischemic brain injury in people suffering migraine.

Postoperative Transient Neurologic Dysfunction: A Proposal for Pathophysiology

BACKGROUND AND PURPOSE: Sudden neurological deterioration which cannot be explained by structural change, ischemia or seizure is often observed among neurosurgical patients. We aimed to provide new insight into the pathophysiology of postoperative transient neurologic dysfunction. METHODS: We describe prolonged but fully reversible focal neurologic dysfunction of unknown origin based on the initial evaluation in 8 patients who had received encephalo-duro-arterio-synangiosis for moyamoya disease. We performed brain imaging, including diffusion weighted imaging and perfusion magnetic resonance imaging or single photon emission computed tomography, and electroencephalography (EEG) during the episodes and after resolution of the symptoms. RESULTS: The symptoms consisted of dysarthria, hemiparesis, or hemiparesthesia of limbs contralateral to the operated side. These symptoms developed between 12 hours and 8 days after surgery and lasted between 12 hours and 17 days. Structural imaging did not show any significant interval change compared with the immediate postoperative images. Perfusion imaging showed increased cerebral blood flow in the symptomatic hemisphere. EEG revealed low amplitude arrhythmic slowing in the corresponding hemisphere. Follow-up imaging and EEG after recovery did not show any abnormalities. CONCLUSIONS: Transient neurologic dysfunction can occur during the postoperative period of brain surgery. Although this may last more than usual transient ischemic attack or seizure, it eventually resolves regardless of treatment. Based on our observation, we propose that this is the manifestation of the transient cortical depression triggered by mechanical stimulation, analogous to migraine aura associated with cortical spreading depression.

Migraine and cerebral small vessel disease / 国际脑血管病杂志

Migraine and cerebral small vessel disease (CSVD) are 2 common neurovascular diseases in clinical practice.Their pathogeneses are still not clear.Migraine may increase the risk of CSVD,and CSVD can also cause migraine attacks by triggering cortical spreading depression and other mechanisms.The relationship between the two diseases is mutual and complex,and is influenced by a variety of factors,but the mechanism of this potential relationship is not yet very clear.With further research,the reports about the relationship between migraine and CSVD are increasing.This article summarizes the pathophysiological mechanisms of migraine and CSVD and the correlation between both.

The effects of flunarizine hydrochloride on plasma calcitonin gene-related peptide and substance P levels after cortical spreading depression in rats / 中国神经精神疾病杂志

Objective To explore the effects of flunarizine hydrochloride on plasma calcitonin gene-related pep-tide and substance P levels after CSD in a rat migraine model of cortical spreading depression (CSD). Methods Thirty adult rats were randomly and evenly divided into three groups:control Group, CSD group and flunarizine group. The CSD waves were evoked by application of potassium chloride on brain surface with filter paper. Funarizine hydrochloride was intravenously administered to rats five minutes prior to application of potassium chloride. The plasma levels of CGRP and SP were measured by using radioimmunity assay. Statistical analyses were performed using two-sample t test and analy-sis of variance. Results CSD waves were absent in control group whereas CSD waves were induced in CSD and flunari-zine groups. The latency of the first CSD wave was longer in flunarizine group (167.90 ± 25.18 s) than in CSD group (130.90 ± 13.30 s) (P<0.01). The number of CSD waves was smaller in flunarizine group (4.50 ± 1.84) than in CSD group (8.50 ± 2.07) (P<0.01). The amplitude of CSD waves was lower in flunarizine group (11.40 ± 4.12 mv) than in CSD group (24.40±3.57 mv) (P<0.01). The levels of CGRP and SP in both CSD group (CGRP, 32.95±11.61 pg/mL;SP, 27.80±7.51 pg/mL) and flunarizine group (CGRP, 25.13 ± 5.67 pg/mL; SP, 19.45 ± 6.10 pg/mL) were higher than in control group (CGRP, 14.44 ± 6.39 pg/mL; SP, 12.36 ± 4.22 pg/mL) (P<0.01). The levels of CGRP and SP in flunarizine group (CGRP, 25.13±5.67 pg/mL;SP, 19.45±6.10 pg/mL) were lower than those in CSD group (CGRP, 32.95±11.61 pg/mL;SP, 27.80± 7.51 pg/mL) (P<0.05). Conclusions Flunarizine hydrochloride can inhibit CSD and reduce the plama levels of CGRP and SP in the rat model of CSD.

Clinical Efficacy of Acute Monitoring Cortical Activity Using Subdural Strip Electrode after Decompressive Craniectomy / 대한신경손상학회지

OBJECTIVE: Decompressive craniectomy is widely used in cases of uncontrolled intracranial hypertension, including traumatic brain injury or acute stroke. Physiological monitorings, such as intracranial pressure or electroenecephalography (EEG) are critical for patients in the acute phase. We retrospectively reviewed our experience of continuous electrocorticography (ECoG) monitoring by subdural strip electrode in patients who performed decompressive craniectomy and assessed its clinical efficacy. METHODS: Patients who underwent decompressive craniectomy because of severe intracranial hypertension were included. 4 Channel strip electrodes were inserted on the frontal cortex before closure. 24-hour continuous monitoring of ECoG was done to identify abnormal electrical activity. The level of consciousness was assessed according to Glasgow Coma Scale (GCS). In patients with malignant intracranial hypertension, barbiturate coma therapy was considered. RESULTS: Fifteen patients (9 men and 6 women) were included and the mean age was 55.7 years (from 17 to 80). The initial mean GCS score was 7.9 (from 3 to 14). In six out of fifteen patients, abnormal spike activities were identified, and one of these six patients was diagnosed as nonconvulsive status epilepticus (NCSE). Cortical spreading depression (CSD) was suspected in five. Three patients underwent barbiturate coma therapy and ECoG monitoring of these patients showed typical burst suppression pattern, which was used for indicator of therapeutic level. The mean duration of strip electrode and ECoG monitoring was 3.5 days, and there was no complication. CONCLUSION: Continuous ECoG monitoring using subdural strip electrode was useful to detect abnormal brain activity in the acute period after decompressive craniectomy.

Animal models of migraine / 国际脑血管病杂志

Migraine is the most common type of primary headache.The ideal animal models of migraine should be able to well replicate the key pathophysiological mechanism of migraine.According to the different pathogeneses,this article reviews the advances in research on the animal models of migraine from the aspect of making methods,determination criterion,advantages and disadvantages,and the scope of application,

Depresiones corticales propagadas y su posible rol en la fisiopatología del daño neuronal subsecuente a la hemorragia subaracnoidea / Cortical spreading depressions and their role in the pathophysiology of neuronal damage subsequent to aneurysmal subarachnoid hemorrhage

El vasoespasmo cerebral es la principal causa potencialmente tratable de mortalidad e incapacidad en pacientes que sufren hemorragia subaracnoidea aneurismática (HSA). Sin embargo, a la fecha no existe un tratamiento eficaz para el mismo. La reciente demostración de la falta de respuesta clínica a la reversión farmacológica del espasmo arterial a consecuencia de HSA ha obligado un replanteo de los fundamentos fisiopatológicos de los déficits neurológicos isquémicos tardíos (“delayed ischemic neurologic déficit”, DIND) a consecuencia de HSA, los cuales se creían en relación al espasmo arterial observado en pacientes con HSA. Desde la demostración de hallazgos electrocorticográficos de depresión cortical propagada (“cortical spreading depression”, CSD) en pacientes con HSA, un interés creciente se ha despertado respecto del rol de estos fenómenos en la fisiopatología de los DIND observados en pacientes con HSA. Cuando inducidas en un cerebro saludable, las CSD se asocian con un aumento del flujo sanguíneo cerebral, facilitando la entrega del cerebro de los sustratos energéticos necesarios. En un cerebro que ha sido lesionado, sin embargo, la CSD se asocia con una reducción en flujo sanguíneo cerebral, lo cual, en el contexto de un aumento de las necesidades de energía, conduce a la insuficiencia energética y la hipoxia, empeorando así el daño cerebral. Estas observaciones sugieren que el déficit de energía producida por la CSD es un factor clave en la patogénesis de los DIND observados a consecuencia de HSA. Este resumen detalla características sobresalientes de las CSD y su potencial relevancia en la fisiopatología del vasoespasmo.

Cerebral vasospasm is the leading potentially treatable cause of mortality and disability in patients with aneurysmatic subarachnoid hemorrhage (SAH). However, to date there is no effective treatment for this entity. The recently demonstrated lack of clinical response to pharmacologic reversal of arterial spasm as a result of SAH has spurred a reassessment of the pathophysiological concepts on delayed ischemic neurologic deficits (DIND) that follow SAH, which were long believed the effect of the arterial spasm observed in patients with SAH. Since the discovery of electrocorticographic cortical spreading depressions (CSD) in patients with SAH, increasing interest has been shown on the role of these phenomena in the pathophysiology of DIND observed in patients with HSA. When induced in a healthy brain, CSD are associated with an increase in cerebral blood flow by facilitating the delivery of the necessary energy substrates. In a brain that has been injured, however, CSD are associated with a reduction in cerebral blood flow, which, in the context of increased energy requirements leads to energy shortage and hypoxia, thus worsening brain damage. These observations suggest that the energetic deficit produced by the CSD is a key factor in the pathogenesis of DIND observed as a result of HSA. This review details striking characteristics of CSD and their potential relevance in the pathophysiology of vasospasm.

Hemorragia subaracnoídea por aneurisma cerebral roto: guías de manejo clínico actualizadas 2010: una propuesta al capítulo vascular de la FLANC / Cortical spreading depressions and their role in the pathophysiology of neuronal damage subsequent to aneurysmal subarachnoid hemorrhage

El vasoespasmo cerebral es la principal causa potencialmente tratable de mortalidad e incapacidad en pacientes que sufren hemorragia subaracnoidea aneurismática (HSA). Sin embargo, a la fecha no existe un tratamiento eficaz para el mismo. La reciente demostración de la falta de respuesta clínica a la reversión farmacológica del espasmo arterial a consecuencia de HSA ha obligado un replanteo de los fundamentos fisiopatológicos de los déficits neurológicos isquémicos tardíos (“delayed ischemic neurologic déficit”, DIND) a consecuencia de HSA, los cuales se creían en relación al espasmo arterial observado en pacientes con HSA. Desde la demostración de hallazgos electrocorticográficos de depresión cortical propagada (“cortical spreading depression”, CSD) en pacientes con HSA, un interés creciente se ha despertado respecto del rol de estos fenómenos en la fisiopatologíade los DIND observados en pacientes con HSA. Cuando inducidas en un cerebro saludable, las CSD se asocian con un aumento del flujo sanguíneo cerebral, facilitando la entrega del cerebro de los sustratos energéticos necesarios. En un cerebro que ha sido lesionado, sin embargo, la CSD se asocia con una reducción en flujo sanguíneo cerebral, lo cual, en el contexto deun aumento de las necesidades de energía, conduce a la insuficiencia energética y la hipoxia, empeorando así el daño cerebral. Estas observaciones sugieren que el déficit de energía producida por la CSD es un factor clave en la patogénesis de los DINDobservados a consecuencia de HSA. Este resumen detalla características sobresalientes de las CSD y su potencial relevancia en la fisiopatología del vasoespasmo.

Cerebral vasospasm is the leading potentially treatable cause of mortality and disability in patients with aneurysmatic subarachnoid hemorrhage (SAH). However, to date there is no effective treatment for this entity. The recently demonstrated lack of clinical response to pharmacologic reversal of arterial spasm as a result of SAH has spurred a reassessment of the pathophysiological concepts on delayed ischemic neurologic deficits (DIND) that follow SAH, which were long believed the effect of the arterial spasm observed in patients with SAH. Since the discovery of electrocorticographic cortical spreading depressions (CSD) in patients with SAH, increasing interest has been shown on the role of these phenomena in the pathophysiology of DIND observed in patients with HSA. When induced in a healthy brain, CSD are associated with an increase in cerebral blood flow by facilitating the delivery of the necessary energy substrates. In a brain that has been injured, however, CSD are associated with a reduction in cerebral blood flow, which, in the context of increased energy requirements leads to energy shortage and hypoxia, thus worsening brain damage. These observations suggest that the energetic deficit produced by the CSD is a key factor inthe pathogenesis of DIND observed as a result of HSA. This review details striking characteristics of CSD and their potential relevance in the pathophysiology of vasospasm.

Acute tryptophan administration impairs cortical spreading depression propagation in REM sleep deprived and non-deprived adult rats

The enhanced availability of tryptophan in the brain, as a consequence of exogenous tryptophan administration, can increase neuronal serotonin synthesis and this can interfere with brain function. REM sleep deprivation (D) constitutes another external factor that can change brain excitability, facilitating, in some cases, the manifestation of neurological diseases like epilepsy. Here we used cortical spreading depression (CSD) as a neurophysiological parameter to investigate the effects of a single L-tryptophan intraperitoneal injection combined or not with 72h D-condition (water-tank technique) in rats. A 1h baseline CSD-recording was performed under urethane+chloralose (1g/kg + 40mg/kg) anesthesia and revealed increased CSD propagation velocities in D rats, as compared with non-deprived (ND), or pseudo-deprived (Pseudo) controls. After the baseline CSD recording, L-tryptophan was immediately injected (125 mg/kg ip, dissolved in water at pH about 3) and this was followed by a significant decrease of CSD propagation velocities, as compared to the baseline values in the same animals of the Pseudo, ND and D condition. In an additional control group (ND rats injected with the vehicle), no CSD propagation change was seen. Our findings indicate an important acute antagonistic influence of tryptophan on CSD propagation, which is not affected by REM sleep deprivation. We suggest that this tryptophan effect may be due to a serotonin-mediated action, probably caused by increased serotonin synthesis as a consequence of enhanced tryptophan availability in the brain.

Pathogenesis of Migraine Aura (review) / 中国康复理论与实践

@#In recent years,many investigations manifested that cortical spreading depression was probably the physiologic foundation of migraine aura.The authors reviewd the relationship between migraine aura and cortical spreading depression.

The Serum Concentration of Matrix Metalloproteinase-9 in Childhood Migraine / 대한소아신경학회지

PURPOSE: Migraine is a common neurological disorder, but the mechanism has not yet been apparently discovered. Recent studies have found that migrainous headache comes from the hemodynamic changes based on the cortical spreading depression and matrix metalloproteinase(MMP)-9 has an important role in this phenomenon. The aim of this study is to investigate the significance of the serum concentration of MMP-9 in children with migraine. METHODS: Among 33 children who visited the headache clinic, from June 2004 to August 2004 we identified and analyzed the clinical findings of 17 patients, who were diagnosed as migraine or tension-type headache. Also we selected 9 children as a healthy control group. The serum concentrations of MMP-9 from all of those were obtained via ELISA kits. RESULTS: The mean duration of headache was 1.3 years in the migraine group. Also, the frequency of migraine is as follows:everyday in 4 patients and more than once during weekdays in 5 patients. The character of headache was throbbing in 8 patients out of 9 patients with migraine. There were no significant differences found in the serum concentrations of MMP-9 between the control group and the migraine group. The serum concentrations of MMP-9 were significantly high, of those who had frequent attacks of migrainous headache. CONCLUSION: The serum concentrations of MMP-9 in the migraine group were not significantly high compared with those in the control group. However, the levels were high from those who complained of migraine frequently. This study suggests that the serum concentration of MMP-9 is not high during a normal period but increases when migraine occurrs.

Cortical Spreading Depression and Migraine / 国际脑血管病杂志

A migraine is a common essential headache in clinical practice. Studies in recent years have found that cortical spreading depression (CSD) may be one of the important mechanisms for the cause of migraine. This article reviews the relationship between SCD and neurobiological mechanism of migraine,particular expounding the significance in the gene mutations of familial hemiplegic migraine, CSD in migraine pathophysiological mechanisms and their prophylactic treatment.

Experimental Study of Initiation of Cortical Spreading Depression by Excitatory Amino Acids Using a New Topical Application Model

The purpose of this study was, first, to devise a new model for topical application of excitatory amino acids(EAAs) to rat cerebral cortex that successfully and repeatdly initiate the cortical spreading depression(CSD). Then, by using this model, six major EAAs that are known to act on single or multiple subtypes of EAA receptor were examined; glutamate, kainate, aspartate, N-methyl-D-aspartate(NMDA), quisqualate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazoie-proprite(AMPA). Through the model, with a cone-shaped well buried in 1.5mm depth of the cerebral cortex, these chemical agents were topically applied to the cortical gray matter. A total of 50 Sprague-Dawley rats were used and divided into seven groups including the sham group. Doses of each EAA between 10(-7) and 10(-4)M concentrations were escalated for triggering the CSD and its rate of consistency in triggering was also evaluated. In the overall results. CSDs were repeatedly initiated in all experimental groups with relatively consistent rates. Duration of CSDs were 1-4 minutes(mean 2.2+/-1.4) and amplitudes were 20-40mV. Effective dose(50)(ED(50)), that trigger over 50% of CSD was 10(-5)M(n=8) for glutamate, 10(-7)M(n=8) for aspartate, 10(-5)M(n=7) for AMPA, 10(-5)M(n=7) for quisqualate, and 10(-4)M(n=7) for NMDA and kainate group. Among those acting on the single receptor, AMPA was shown to be the most effective in triggering CSD, and NMDA, and kainate were in descending orders. Aspartate that was known to act on multiple EAA receptors, showed the highest rate of triggering CSD among all groups, but glutamate, known to act on all receptors of its subtypes, showed the most consistent rate of triggering CSD at dose escalation. These results revealed that those EAA acting on multiple receptors, namely aspartate and glutamate, showed the highest and most consistent rate of triggering CSD. Among those acting on single channel of receptors. AMPA was the most effective, although its consistency and rate of triggering of CSD was somewhat lower than.

Correlation between Periinfaret Cortical Spreading depression and Ischemic Volume in Rats

Cortical spreading Depression(CSD) is a transient depression of neuronal activity that spreads across the cortical surface and is associated with profound changes in blood flow, extracellular ion concentration. Direct Current(DC) potentials and cell membrane potentials. One of the electrophysiological disturbance in the periinfarct surrounding is spontaneous occurrence of repeated CSD like DC shifts associated with increased energy demand. Due to restricted blood flow to the periinfarct border zone, elevated metabolic demand is potentially hazardous. So the authors designed this experiment to verify the correlation between periinfarct cortical spreading depression and ischemic volume following permanent middle cerebral artery(MCA) occlusion in rats. Sprague-Dawley rats(n=27) were anesthetized with 0.5~1% halothane, and artificially ventilated through a tracheal cannula. Arterial pressure, blood gases and body temperature were controlled. The middle cerebral artery(MCA) was occluded distally to the lenticulostriate branches. Measurements of CSD activity were made for 4 hours in each animal infarct volume was determined 6 hours later in 2,3,5-triphenyl tetrazolium chloride(TTC)- stained section. For 4 hours after MCA occlusion, the CSDs were found in all experimental animals with a range of 2~9 times. Those CSDs were of varying duration: "small"(1min) SDs and mean of total duration of SD was 10.5+/-10.3 min during 4 hours of MCA occlusion. Neuropathological evaluation of brain infarct in the rats, which had been allowed to survive for 6 hours after MCA occlusion showed a mean volume of 89.7+/-45.3 mm3. Serial observation of duration of CSD prologation of duration of CSD nor the frequency of CSD in the penumbral zone correlated with the volume of infarct.However total duration of CSD was slightly related with the infarct volume after 6 hours of the permanent MCA occlusion(r=0.414, p=0.0318) .

The Changes of Cortical Spreading Depression During Hypothermia and Rewarming in Rat

The present study was carried out to evaluate the effect of hypothermia and rewarming on the pattern of Cortical Spreading Depression(CSD) and predict the resultant vulnerability of the brain. Thirty four Sprague-Dawley rats, either sex, weighing 250-350gm, were used. They were devided into 4 groups, according to the degree of hypothermia and speed of rewarming, Profound Hypothermia & Slow Rewarming(G I), Profound Hypothermia & Rapid Rewarming(G II), Moderate Hypothermia & Slow Rewarming(G III), Moderate Hypothermia & Rapid Rewarming(G IV). CSD was elicited by local application of KC1 and identified by Direct Current Potential(DCP). We estimated the Frequency of DCP, Recovery time of negative shift of DCP, Area of negative shift of DCP according to the change of body temperature. The frequencies of DCP increased after rewarming compared with the normothermic state in all groups, statistical significance(P<0.05) was specially evident in Group II(Profound Hypothermia & Rapid Rewarming group), 5.1+/-0.3/30min.(mean+/-standard error) in normothermic state, while 9.3+/-0.8/30min in rewarming state. Recovery time(width) of DCP was delayed with hypothermia but decreased with rewarming but delayed state compared with normothermic state in all groups, i.e. 34.7+/-1.0sec at normothermic state, 59.9+/-4.3sec at 27.5 degrees C, 40+/-1.4sec at rewarming state in Group II. We can predict that the vulnerability of the brain tissue may be increased during the rewarming state following hypothermia in all groups. Such evidence is more significant in Group II(Profound Hypothermia & Rapid Rewarming) during the period of certain time(30-60min) after rewarming.

Influence of Hypoglycemia and Hypothermia on Direct Current Potential During Cortical Spreading Depression in Rats

The object of this study was to investigate the influences of hypoglycemia and hypothermia on the direct current(DC) pontetial changes during cortical spreading depression(CSD) in rats. The induction of CSD was achieved by the application of KCI solution on the cortex of the frontal lobe. Hypoglycemia and hypothermia were induced respectively by insulin injection and the application of an ice pack. The DC potential changes during progressive hypoglycemia and hypothermia were measured with microelectrodes from the cortex of the parietal lobe of rats. Under contril condition, the rate of CSD was one per 5-10 min and the negative shift of DC potential was about 30 mV. The recovery time from negative shift to base line of DC potential was about 40 sec. In rats treated with insulin, the amplitude of DC potential shift was unaffected by hypoglycemia. The recovery time of DC shift was 40+/-2.26 sec at normoglycemia and it was delayed progressively as the blood glucose level lowered. The mean of it was 63+/-8.02 sec at 30 mg/dl and 77.1+/-22.0 sec with the blood glucose falling below 20 mg/dl. The same delay in the recovery time as seen in the hypogylcemia group was observed in rats treated with hypothermia. The recovery time of DC shift was 39.4+/-3.02 sec in normothermia(36.5degrees C), but it was delayed to 61.15+/-4.15 sec at 30degrees C and 96.67+/-14.92 sec at 26degrees C body temperature. This study suggested that each condition of profound hypoglycemia below 30 mg/dl and hypothermia below 30degrees C was to be harmful to the ion homeostasis and the integrity of the cell membrane and it may lead neurons to death.