• Journal of Korean Neurosurgical Society
• /
• v.55 no.3
• /
• pp.125-130
• /
• 2014

Objective : This study was conducted to elucidate neuroprotective effect of carnosine in early stage of stroke. Methods : Early stage of rodent stroke model and neuroblastoma chemical hypoxia model was established by middle cerebral artery occlusion and antimycin A. Neuroprotective effect of carnosine was investigated with 100, 250, and 500 mg of carnosine treatment. And antioxidant expression was analyzed by enzyme linked immunosorbent assay (ELISA) and western blot in brain and blood. Results : Intraperitoneal injection of 500 mg carnosine induced significant decrease of infarct volume and expansion of penumbra (p<0.05). The expression of superoxide dismutase (SOD) showed significant increase than in saline group in blood and brain (p<0.05). In the analysis of chemical hypoxia, carnosine induced increase of neuronal cell viability and decrease of reactive oxygen species (ROS) production. Conclusion : Carnosine has neuroprotective property which was related to antioxidant capacity in early stage of stroke. And, the oxidative stress should be considered one of major factor in early ischemic stroke.

• Biomolecules & Therapeutics
• /
• v.30 no.1
• /
• pp.55-63
• /
• 2022

Oleanolic acid (OA), a natural pentacyclic triterpenoid, has been reported to exert protective effects against several neurological diseases through its anti-oxidative and anti-inflammatory activities. The goal of the present study was to evaluate the therapeutic potential of OA against acute and chronic brain injuries after ischemic stroke using a mouse model of transient middle cerebral artery occlusion (tMCAO, MCAO/reperfusion). OA administration immediately after reperfusion significantly attenuated acute brain injuries including brain infarction, functional neurological deficits, and neuronal apoptosis. Moreover, delayed administration of OA (at 3 h after reperfusion) attenuated brain infarction and improved functional neurological deficits during the acute phase. Such neuroprotective effects were associated with attenuation of microglial activation and lipid peroxidation in the injured brain after the tMCAO challenge. OA also attenuated NLRP3 inflammasome activation in activated microglia during the acute phase. In addition, daily administration of OA for 7 days starting from either immediately after reperfusion or 1 day after reperfusion significantly improved functional neurological deficits and attenuated brain tissue loss up to 21 days after the tMCAO challenge; these findings supported therapeutic effects of OA against ischemic stroke-induced chronic brain injury. Together, these findings showed that OA exerted neuroprotective effects against both acute and chronic brain injuries after tMCAO challenge, suggesting that OA is a potential therapeutic agent to treat ischemic stroke.

• Progress in Medical Physics
• /
• v.21 no.4
• /
• pp.348-353
• /
• 2010

The purpose of this study was to explore the potentials of a clinical 3T MRI in mouse brains and technical adaptation and optimization. T1-weighted images (T1WI), T2-weighted images (T2WI), FLAIR (Fluid Attenuated Inversion Recovery) images, Gadolinium enhanced T1-weighted images (Gd-T1WI), Diffusion weighted images (DWI) were acquired in brain of 2 mice (weight 20~25 g) with cerebral infarction by occlusion of right middle cerebral artery, 1 hour, 24 hours, 72 hours after infarction and 1 normal mouse brain using clinical 3T MRI scanner. We analyzed differentiation of striatum, ventricle, cerebral cortex, and possibility of detection of acute cerebral infarction. We could differentiate the striatum, ventricle, cerebral cortex on T2WI and on DWI, FLAIR, T1WI, the differentiation of each anatomy of brain was not definite, but acute cerebral infarction was detected on DWI of 1 hour, 24 hours, 72 hours after infarction and on T2WI, FLAIR of 24 hours, 72 hours after infarction. Clinical 3T MRI can be used in differentiation of anatomy of mouse brains and DWI can be helpul in detection of acute cerebral infarction in acute phase. With technical adaptation and optimization clinical 3T MRI can be useful tool for provide preclinical and clinical small animal studies.

• The Korean Journal of Pain
• /
• v.21 no.2
• /
• pp.119-125
• /
• 2008

Background: Cerebral blood vessels are innervated by sympathetic nerves from the superior cervical ganglia (SCG), and these nerves may influence the cerebral blood flow. The purpose of the present study was to evaluate the neuroprotective effect of superior cervical sympathetic ganglion block in rats that were subjected to focal cerebral ischemia/reperfusion injury. Methods: Eighty male Sprague-Dawley rats (270-320 g) were randomly assigned to one of two groups (the ropivacaine group and a control group). In all the animals, brain injury was induced by middle cerebral artery (MCA) reperfusion that followed MCA occlusion for 2 hours. The animals of the ropivacaine group received $30{\mu}l$ of 0.75% ropivacaine, and their SCG. Neurologic score was assessed at 1, 3, 7 and 14 days after brain injury. Brain tissue samples were then collected. The infarct ratio was measured by 2.3.5-triphenyltetrazolium chloride staining. The terminal deoxynucleotidyl transferase mediated dUTP-biotin nick-end labeled (TUNEL) reactive cells and the cells showing caspase-3 activity were counted as markers of apoptosis at the caudoputamen and frontoparietal cortex. Results: The death rate, the neurologic score and the infarction ratio were significantly less in the ropivacaine group 24 hr after ischemia/reperfusion injury. The number of TUNEL positive cells in the ropivacaine group was significantly lower than those values of the control group in the frontoparietal cortex at 3 days after injury, but the caspase-3 activity was higher in the ropivacaine group than that in the control group at 1 day after injury. Conclusions: The study data indicated that a superior cervical sympathetic ganglion block may reduce the neuronal injury caused by focal cerebral ischemia/reperfusion, but it may not prevent the delayed damage.

• The Korean Journal of Pain
• /
• v.20 no.2
• /
• pp.83-91
• /
• 2007

Background: Cerebral blood vessels are innervated by sympathetic nerves that originate in the superior cervical ganglia (SCG). This study was conducted to determine the effect of an SCG block on brain injury caused by focal cerebral ischemia/reperfusion in a rat model. Methods: Male Sprague-Dawley rats (270-320 g) were randomly assigned to one of three groups (lidocaine, ropivacaine, and control). After brain injury induced by middle cerebral artery (MCA) occlusion/reperfusion, the animals were administered an SCG bloc that consisted of $30{\mu}l$ of 2% lidocaine or 0.75% ropivacaine, with the exception of animals in the control group, which received no treatment. Twenty four hours after brain injury was induced, neurologic scores were assessed and brain samples were collected. The infarct and edema ratios were measured, and DNA fragmented cells were counted in the frontoparietal cortex and the caudoputamen. Results: No significant differences in neurologic scores or edema ratios were observed among the three groups. However, the infarct ratio was significantly lower in the ropivacaine group than in the control group (P < 0.05), and the number of necrotic cells in the caudoputamen of the ropivacaine group was significantly lower than in the control group (P < 0.01). Additionally, the number of necrotic and apoptotic cells in theropivacaine group were significantly lower than inthe control group in both the caudoputamen and the frontoparietal cortex (P < 0.05). Conclusions: Brain injury induced by focal cerebral ischemia/reperfusion was reduced by an SCG block using local anesthetics. This finding suggests that a cervical sympathetic block could be considered as another treatment option for the treatment of cerebral vascular diseases.

• The Journal of the Korea Contents Association
• /
• v.9 no.2
• /
• pp.309-317
• /
• 2009

This study was to investigate the effects of restoring cognition function and neurotrophic factor in the hippocampus according to memory and learning training in rats affected by brain injury. Brain injury was induced in Sprague-Dawley rats(36 rats) through middle cerebral artery occlusion(MCAo). And then experiment groups were randomly divided into three groups; Group I: Brain injury induction(n=12), Group II: the application for treadmill training after brain injury induction(n=12), Group III: the application for memory and learning training after brain injury induction(n=12). Morris water maze acquisition test and retention test were performed to test cognitive function. And the histological examination was also observed through the immunohistochemistric response of BDNF(brain-derived neurotrophic factor) in the hippocampus. For Morris water maze acquisition test, there were significant interactions among the groups with the time(p<.001). The time to find the circular platform in Group III was more shortened than in Group I, II on the 9th, 10th, 11th and 12th day. For Morris water maze retention test, there were significant differences among the groups(p<.001). The time to dwell on quadrant circular platform in Group III on the 13th day was the longest compared with other groups. And as the result of observing the immunohistochemistric response of BDNF in the hippocampus CA1, the response of immunoreactive positive in Group III on the 7th day increased more than that of Group I, II. These results suggested that the memory and learning training in rats with brain injury has a more significant impact on restoring cognitive function via the changes of neurotropic factor expression and synaptic neuroplasticity.

• Journal of Acupuncture Research
• /
• v.33 no.4
• /
• pp.49-63
• /
• 2016

Objectives : This research was performed to investigate the effects of Jodeungsan pharmacopuncture(PA-J) of focal brain ischemia induced by middle cerebral artery occlusion(MCAO) in rats. Methods : The subjects were divided into 4 groups : control, acupuncture, pharmacopuncture PA-J1(11.43 mg / 250 g / $40{\mu}{\ell}$) and pharmacopuncture PA-J2(2.29 mg / 250 g / $40{\mu}{\ell}$). The focal brain ischemia was induced by intraluminal filament insertion into the middle cerebral artery. After 3 days of MCAO, Jodeungsan pharmacopuncture treatment was performed on the GB20, and the day after being treated with pharmacopuncture, the Morris water maze test was carried out on the assigned group. The series of processes were administered 6 times. Thereafter mGluR5, density of neuronal cell and ChAT were measured. Results : The results were as follows. 1. The distance to target significantly decreased in the 2nd trial of the Acu group on the water maze test for short-term memory. 2. The distance to target significantly decreased in the 4th trial of the PA-J2 group on the water maze test for long-term memory. 3. The intensity of mGluR5 significantly increased in the PA-J1 group compared with the control group. 4. The neuroprotective effect on the hippocampal CA1 significantly increased in the PA-J1 and PA-J2 groups compared with the control group. 5. The density of ChAT in the hippocampal CA1 significantly increased in the PA-J1 and PA-J2 groups compared with the control group. Conclusion : These results suggest that Jodeungsan pharmacopuncture may improve memory and cognitive impairment and also have neuroprotective effects on focal brain ischemia.

• Journal of Korean Neurosurgical Society
• /
• v.65 no.5
• /
• pp.665-679
• /
• 2022

Objective : Patients with mild ischemic stroke experience various sequela and residual symptoms, such as anxious behavior and deficits in movement. Few approaches have been proved to be effective and safe therapeutic approaches for patients with mild ischemic stroke by acute stroke. Sildenafil (SIL), a phosphodiesterase-5 inhibitor (PDE5i), is a known remedy for neurodegenerative disorders and vascular dementia through its angiogenesis and neurogenesis effects. In this study, we investigated the efficacy of PDE5i in the emotional and behavioral abnormalities in rats with mild ischemic stroke. Methods : We divided the rats into four groups as follows (n=20, respectively) : group 1, naïve; group 2, middle cerebral artery occlusion (MCAo30); group 3, MCAo30+SIL-pre; and group 4, MCAo30+SIL-post. In the case of drug administration groups, single dose of PDE5i (sildenafil citrate, 20 mg/kg) was given at 30-minute before and after reperfusion of MCAo in rats. After surgery, we investigated and confirmed the therapeutic effect of sildenafil on histology, immunofluorescence, behavioral assays and neural oscillations. Results : Sildenafil alleviated a neuronal loss and reduced the infarction volume. And results of behavior task and immunofluorescence shown possibility that anti-inflammation process and improve motor deficits sildenafil treatment after mild ischemic stroke. Furthermore, sildenafil treatment attenuated the alteration of theta-frequency rhythm in the CA1 region of the hippocampus, a known neural oscillatory marker for anxiety disorder in rodents, induced by mild ischemic stroke. Conclusion : PDE5i as effective therapeutic agents for anxiety and movement disorders and provide robust preclinical evidence to support the development and use of PDE5i for the treatment of mild ischemic stroke residual disorders.

• The Korean Journal of Physiology and Pharmacology
• /
• v.12 no.5
• /
• pp.275-280
• /
• 2008

A brief ischemic insult induces significant protection against subsequent massive ischemic events. The molecular mechanisms known as preconditioning (PC)-induced ischemic tolerance are not completely understood. We investigated whether kinetic changes of cyclooxygenase (COX)-2 during reperfusion time-periods after PC were related to ischemic tolerance. Rats were given PC by occlusion of middle cerebral artery (MCAO) for 10 min and sacrificed after the indicated time-periods of reperfusion (1, 2, 4, 8, 12, 18 or 24 h). In PC-treated rats, focal ischemia was induced by occlusion of MCA for 24 h and brain infarct volume was then studied to determine whether different reperfusion time influenced the damage. We report that the most significant protection against focal ischemia was obtained in rats with 8 h reperfusion after PC. Administration of indomethacin (10 mg/kg, oral) or rofecoxib (5 mg/kg, oral) 48 h prior to PC counteracted the effect of PC. Immunohistochemical analysis showed that COX-2 and HO-l protein were induced in PC-treated rat brain, which was significantly inhibited by rofecoxib. Taken together, we concluded that the kinetic changes of COX-2 expression during the reperfusion period after PC might be partly responsible for ischemic tolerance.

• Transactions on Electrical and Electronic Materials
• /
• v.16 no.2
• /
• pp.65-69
• /
• 2015

Low level laser therapy (LLLT) has facilitated an improvement in acupuncture treatment. In this study, we stimulated Shaochong (HT9), Dadun (LR1), Shaohai (HT3), and Yingu (KI10) acupoints with pulsed laser diodes 532 nm [green laser] and 658 nm [red laser] in rats with induced middle cerebral artery occlusion(MCAO). The animals were divided into 6 groups: intact control; MCAO control without LLLT; LLLT with red laser at HT9·LR1 and HT3·KI10 (RR); LLLT with green laser at HT9·LR1 and HT3·KI10 (GG); LLLT with green laser at HT9·LR1 and red laser at HT3·KI10 (GR); and LLLT with red laser at HT9·LR1 and green laser at HT3·KI10 (RG). We evaluated the immunohistochemical changes in the hippocampal CA1 region, and complete blood count changes. Compared to the MCAO control group, the RG group showed a significant decrease in Bax and cytochrome c levels in the hippocampus, and a significant increase in hemoglobin level, hematocrit, total white blood cell, neutrophil, lymphocyte, monocyte, and erythrocyte counts.