• Journal of Korean Neurosurgical Society
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• 제30권7호
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• pp.831-841
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• 2001

Objective : Somatosensory evoked potentials(SSEPs) have been used widely both experimentally and clinically to monitor the function of central nervous system and peripheral nervous system. Studies of SSEPs have reported the various recording techniques and patterns of SSEP. The previous SSEP studies used scalp recording electrodes, showed mean vector potentials which included relatively constant brainstem potentials(far-field potentials) and unstable thalamocortical pathway potentials(near-field potentials). Even in invasive SSEP recording methods, thalamocortical potentials were variable according to the kinds, depths, and distance of two electrodes. So they were regarded improper method for monitoring of upper level of brainstem. The present study was conducted to investigate the characteristics of somatosensory evoked field potentials(SSEFPs) of the cerebral cortex that evoked by hindlimb stimulation using ball electrode and the pathways of SSEFP by recording the potentials simultaneously in the cortex, VPL nucleus of thalamus, and nucleus gracilis. Methods : In the first experiment, a specially designed recording electrode was inserted into the cerebral cortex perpendicular to the cortical surface in order to recording the constant cortical field potentials and SSEFPs mapped from different areas of somatosensory cortex were analyzed. In the second experiment, SSEPs were recorded in the ipsilateral nucleus gracilis, the contralateral ventroposterolateral thalamic nucleus(VPL), and the cerebral cortex along the conduction pathway of somatosensory information. Results : In the first experiment, we could constantly obtain the SSEFPs in cerebral cortex following the transcutaneous electrical stimulation of the hind limb, and it revealed that the first large positive and following negative waves were largest at the 2mm posterior and 2mm lateral to the bregma in the contralateral somatosensory cortex. The second experiment showed that the SSEPs were conducted by way of posterior column somatosensory pathway and thalamocortical pathway and that specific patterns of the SSEPs were recorded from the nucleus gracilis, VPL, and cerebral cortex. Conclusion : The specially designed recording electrode was found to be very useful in recording the localized SSEFPs and the transcutaneous electrical stimulation using ball electrode was effective in evoking SSEPs. The characteristic shapes, latencies, and conduction velocities of each potentials are expected to be used the fundamental data for the future study of brain functions, including the hydrocephalus model, middle cerebral artery ischemia model, and so forth.

• Journal of Korean Neurosurgical Society
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• 제29권10호
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• pp.1289-1295
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• 2000

Purpose : Recent evidence suggests a possible role for leukocytes in brain injury following ischemia and reperfusion. This study examined the temporal profile of ischemic tissue damage and leukocyte response after transient middle cerebral artery occlusion(MCAO) with reperfusion in the mouse. Methods : Focal cerebral ischemia was made by temporary occluding of the stem of the proximal MCA. Two groups of the mouse were investigated : (1) sham operation(n＝10), and (2)those having the arterial occlusion released after 90 minute(n＝20). By 4 hours(n＝10) and 24 hours(n＝10) after the onset of ischemia-reperfusion, fluorescein videoimages were under-taken in the pial venules of the mouse using a closed cranial window technique. Rhodamine 6G was administered as a $80-100{\mu}l/min$ i.v. loading dose and a $30-40{\mu}l/min$ i.v. maintenance dose in saline to selectively label circulating leukocytes. Neuropathologic evaluation for brain injury was accomplished using the histochemical stain 2,3,5-triphen-yltetrazolium chloride(TTC) and hematoxylin and eosin(H & E) stain. Results : The mean number of adherent leukocytes to cerebral venules in the 90 minutes MCAO and 24 hours reperfusion group were $306{\pm}24$ compared with $72{\pm}8$ in the sham operation group. In the TTC staining method, the cortical infarct affecting 34.8% of hemispheric volume were created in all of animals (n＝10) undergoing 90 minute MCAO with 24 hours reperfusion, but the infarcted area were not found in the other(sham operation and 90 minute MCAO with 4 hours reperfusion)groups. In the H & E stain, the brain tissue following 90 minute MCAO with 4 hours reperfusion revealed only a pyknosis of the nuclei with shrunken cytoplasm, but infiltrated leukocytes were not observed. After 24 hours of reperfusion, a many leukocytes were infiltrated within parenchyma and blood vessles. Conclusions : These findings demonstrate the feasiblity of continous in vivo monitoring of leukocyte adherence in cerebral venules and suggest that reperfusion induced leukocyte adherence to venular endothelium may contribute to tissue injury following focal cerebral ischemia.

• The Korean Journal of Physiology
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• 제23권1호
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• pp.43-49
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• 1989

Atrial natriuretic peptide (ANP)의 혈압조절에 대한 효과를 구명하기 위하여 2-kidney, 1-clip 흰쥐의 고혈압 발생에 미치는 ANP의 영향을 조사하였다. 실험군은 왼쪽 신동맥에 clip을 끼우고 경정맥내에 지속적으로 ANP를 주입한(atriopeptin III, 500 ng/h) 군으로 하였으며, 대조군은 clip을 끼웠으나 ANP를 주입하지 않은 군으로 하였다. Clip을 끼우기 전과 clip을 끼운 제 4,7,10일에 꼬리동맥으로부터 혈압을 측정한 후 단두하여 혈액을 채취하고 양측 신장을 떼어내어 renin 치를 구하였다. ANP 주입군은 대조군에 비하여 고혈압의 발생이 약화되었고 혈장 renin활성도가 유의하게 낮았으나 신피질 renin함량은 양군간에 유의한 차이가 없었다. 한편 clip을 끼우지 않은 흰쥐에서는 ANP 주입군과 비주입군간에 혈압, 혈장 renin 활성도와 신피질 renin 함량 등이 모두 서로 유의한 차이를 보이지 않았다. 이상의 실험결과는 지속적 ANP 주입이 2-K, 1-C 흰쥐의 고혈압 발생을 방지하지는 못하였으나 약화시켰음을 보여주었으며, ANP는 적어도 부분적으로는 renin-angiotensin계를 길항하므로써 장기적 혈압 조절에 관여하는 것이 시사되었다.

• The Korean Journal of Physiology
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• 제30권1호
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• pp.33-41
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• 1996

The present study was aimed to investigate the role of endothelium-derived nitric oxide (NO) in the control of renin release and to examine if NO is implicated in the development of two-kidney, one clip (2K1C) hypertension. Male Sprague-Dawley rats $(150{\sim}200\; g)$ were constricted at the left renal artery. They were then supplemented with $N^{G}-nitro-L-arginine\;methyl\;ester\;(L-NAME,\; 5mg/100\;mL)$ or with L-arginine hydrochloride (400 mg/100 mL) in the drinking water. The control group was supplied with normal tap water. The sham-clipped rats were operated as in 2K1C rats except for that no clip was made. The kidneys were taken to examine in vitro release of renin at days 7 and 14 following clipping the renal artery. Northern blot analysis was also done to assess the expression of renin gene in the kidney. In sham-clipped rats, L-NAME caused a sustained increase of the blood pressure, whereas L-arginine was without effect. Neither L-NAME nor L-arginine-supplementation significantly affected the development of hypertension in 2K1C rats. Plasma renin concentration (PRC) measured on day 28 did not significantly differ among the L-NAME, L-arginine and control groups either in 2K1C or in sham-clipped rats. Renin contents (RRC) in the clipped kidney were increased, while those in the contralateral kidney were decreased. The release of renin in vitro from cortical slices was also enhanced in the clipped kidney, whereas it was attenuated in the contralateral. Comparing the RRC and in vitro release, the latter was more rapidly decreased than the former in the contralateral kidney. The renin mRNA levels in the contralateral kidney were almost at their nadir at days 7 and 14 in 2K1C rats. It is suggested that NO does not affect the development of 2K1C hypertension in which the renin-angiotensin system has been activated. The data also confirm that RRC and renin gene expression are increased in the clipped kidney and suppressed in the contralateral kidney in 2K1C rats.

• 한국감성과학회:학술대회논문집
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• 한국감성과학회 2009년도 추계학술대회
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• pp.183-185
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• 2009

As imaging technology develops, magnetic resonance imaging (MRI) techniques have contributed to the understanding of brain function by providing anatomical structure of the brain and functional imaging related to information processing. Manganese-enhanced MRI (MEMRI) techniques can provide useful information about functions of the nervous system. However, systematic studies regarding information processing of pain have not been conducted. The purpose of this study was to detect brain activation during painful electrical stimulation using MEMRI with high spatial resolution. Male Sprague-Dawley rats (250-300 g) were divided into 3 groups: normal control, sham stimulation, and electric stimulation. Rats were anesthetized with 2.5% isoflurane for surgery. Polyethylene catheter (PE-10) was placed in the external carotid artery to administrate mannitol and MnCl2. The blood brain barrier (BBB) was broken by 20% D-mannitol under anesthesia mixed with urethane and a-chloralose. The hind limb was electrically stimulated with a 2Hz (10V) frequency while MnCl2 was infused. Brain activation induced by electrical stimulation was detected using a 4.7 T MRI. Remarkable signal enhancement was observed in the primary sensory that corresponds to sensory tactile stimulation at the hind limb region. These results suggest that signal enhancement is related to functional activation following electrical stimulation of the peripheral receptive field.

• 동의생리병리학회지
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• 제27권2호
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• pp.173-182
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• 2013

This Study was designed to investigate the effects of Sibjeondaebo-tang (SDT) and Gamy-Sibjeondaebo-tang (GST, Sibjeondaebo-tang adding Cervi Pantotrichum Cornu) on the improvement in regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP) in normal rats, and in the rats with cerebral ischemia induced by middle cerebral artery occlusion, and further to determine the mechanisms. And, It was to investigate the effects of the SDT and GST with the change of histologic examination through the BDNF in the hippocampus CA1. In changes of cerebral hemodynamics, SDT and GST significantly increased rCBF in a dose-dependent manner but decreased MABP in normal rats. In mechanism of cerebral hemodynamics, Increase of GST-induced rCBF was significantly inhibited by pretreatment with methylene blue (0.01 mg/kg, i.p.), an inhibitor of guanylate cyclase, and Decrease of GST-induced MABP was significantly increased by pretreatment with methylene. These results suggested that the action of GST was mediated by guantlate cyclase pathway. In cerebral ischemics, the rCBF was stably improved by SDT (10 mg/kg, i.p.) significantly and stably increased by GST (10 mg/kg, i.p.) during the period of cerebral reperfusion, which contrast with the findings of rapid and marked increase in Control group. These results suggested that GST had anti-ischemic action in cerebral ischemic state. In histological examination through TTC stain, Sample A group and Sample B group decreased discoloration in the cortical part at $28^{th}$ day after MCAO induction. In immunohistochemistric response of BDNF, Sample A group and Sample B group increased respondent effect at $28^{th}$ day after MCAO induction. These results suggest that GST can Increase rCBF in normal state, as well as improve the stability of rCBF in cerebral ischemic state. Furthermore, methylene blue inhibitor study suggested the mechanism of blood flow enhancement by GST may be mediated by guanylate cyclase pathway.

• 대한의용생체공학회:의공학회지
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• 제28권3호
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• pp.338-343
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• 2007

BOLD T2*-weighted MR images reflects cortical blood flow and oxygenation alterations. fMRI study relies on the detection of localized changes in BOLD signal intensity. Since fMRI measures the very small modulations in BOLD signal intensity that occur during changes in brain activity, it is also very sensitive to small signal intensity variations caused by physiologic noise during the scan. Due to the complexity of movement of various organs associated with heart beat, it is important to reduce cardiac related noise rather than other physiological noise which could be required with relatively simple method. Therefore, a number of methods have been developed for the estimation and reduction of cardiac noise in fMRI study. But, each method has limitation. In this study, we proposed a new estimation method for brain activities influenced by blood pulsation effect using regression analysis with blood pulsation signal and the correspond slice of fMRI. We could find out that the right anterior cingulate cortex and right olfactory cortex and left olfactory cortex were largely influenced by blood pulsation effect for new method. These observed areas are mostly on the structure of anterior cerebral artery in the brain. That is convinced with that our method would be valid and our new method is easier to apply in practice and reduce computational burden than the retrospective method.

• The Korean Journal of Physiology and Pharmacology
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• 제14권6호
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• pp.435-440
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• 2010

Valproic acid (VPA) is a well-known anti-epileptic and mood stabilizing drug. A growing number of reports demonstrate that VPA is neuroprotective against various insults. Despite intensive efforts to develop new therapeutics for stroke over the past two decades, all treatments have thus far failed to show clinical effect because of treatment-limiting side effects of the drugs. Therefore, a safety-validated drug like VPA would be an attractive candidate if it has neuroprotective effects against ischemic insults. The present study was undertaken to examine whether pre- and post-insult treatments with VPA protect against brain infarct and neurological deficits in mouse transient (tMCAO) and permanent middle cerebral artery occlusion (pMCAO) models. In the tMCAO (2 hr MCAO and 22 hr reperfusion) model, intraperitoneal injection of VPA (300 mg/kg, Lp.) 30 min prior to MCAO significantly reduced the infarct size and the neurological deficit. VPA treatment immediately after reperfusion significantly reduced the infarct size. The administration of VPA at 4 hr after reperfusion failed to reduce the infarct size and the neurological deficit. In the pM CAO model, treatment with VPA (300 mg/kg, i.p.) 30 min prior to MCAO significantly attenuated the infarct size, but did not affect the neurological deficit. Western blot analysis of acetylated H3 and H4 protein levels in extracts from the ischemic cortical area showed that treatment with VPA increased the expression of acetylated H3 and H4 at 2 hrs after MCAO. These results demonstrated that treatment with VPA prior to ischemia attenuated ischemic brain damage in both mice tMCAO and pMCAO models and treatment with VPA immediately after reperfusion reduced the infarct area in the tMCAO model. VPA could therefore be evaluated for clinical use in stroke patients.

• Journal of Korean Neurosurgical Society
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• 제40권3호
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• pp.180-185
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• 2006

Objective : Middle cerebral artery occlusion[MCAO] has widely been used to produce ischemic brain lesions. The lesions induced by MCAO tend to be variable in size because of the variance in the collateral blood supply found in the mouse brain. To establish a less invasive and reproducible focal ischemia model in mice, we modified the technique used for rat photo thrombosis model. Methods : Male C57BL/6 mice were subjected to focal cerebral ischemia by photothrombosis of cortical microvessels. Cerebral infarction was produced by intraperitoneal injection of Rose Bengal, a photosensitive dye and by focal illumination through the skull. Motor impairment was assessed by the accelerating rotarod and staircase tests. The brain was perfusion-fixed for histological determination of infarct volume four weeks after stroke. Results : The lesion was located in the frontal and parietal cortex and the underlying white matter was partly affected. A relatively constant infarct volume was achieved one month after photothrombosis. The presence of the photothrombotic lesion was associated with severe impairment of the motor performance measured by the rotarod and staircase tests. Conclusion : Photothrombotic infarction in mice is highly reproducible in size and location. This procedure can provide a simple method to produce cerebral infarction in a unilateral motor cortex lesion. In addition, it can provide a suitable model for study of potential neuroprotective and therapeutic agents in human stroke.

• The Korean Journal of Physiology and Pharmacology
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• 제2권5호
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• pp.573-580
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• 1998

The study aims to identify the mechanism (s) underlying the altered vasodilatory responses of the pial artery of spontaneously hypertensive rats (SHR) under a hypothesis that calcitonin gene-related peptide (CGRP) exerts a modulator role in the autoregulation of cerebral blood flow (CBF). The animals were divided into four groups: 1) Sprague-Dawley rats (SDR), 2) Wistar rats (WR), 3) SHR with high blood pressure $(BP{\ge}150\;mmHg),$ and 4) SHR with normotensive BP $({\le}150\;mmHg).$ The lower limit of CBF autoregulation in SHR shifted to a higher BP $(82.8{\pm}9.3\'mmHg,\;P<0.05)$ than that in SDR $(58.9{\pm}5.7\;mmHg)$. In SHR, whether the BP levels were high or normotensive, the vasodilator responses to a stepwise hypotension were significantly attenuated unlike with SDR and WR. When artificial cerebrospinal fluid (CSF) containing capsaicin $(3{\times}10^{-7}\;M)$ was suffused over the cortical surface, a transient increase in pial arterial diameter was observed in the SHR with high or normotensive BP. In contrast, SDR and WR showed a large increase in diameter, and the increase was sustained for over 10 minutes. In line with these results, the basal releases of CGRP-like immunoreactivity (CGRP-LI) in the isolated pial arteries from SHR with high and normotensive BP were $12.5{\pm}1.4\;and\;9.8{\pm}2.8\;fmole/mm^2/60\;min\;(P<0.05)$, while those from SDR and WR were $25.5{\pm}3.1\;and\;24.6{\pm}3.1\;fmole/mm^2/60\;min,$ respectively. The isolated basilar arteries showed similar results to those of the pial arteries in SHR. Thus, it is summarized that, in the SHR, the reduced autoregulatory vasodilator responses to stepwise hypotension and capsaicin may be, in part, ascribed to the decreased release of CGRP from the perivascular sensory nerve fibers of the pial arteries, and that altered vasomotor activity in SHR may not be related with the hypertensive tone.