Histological changes of neuronal damage in vegetative dogs induced by 18 minutes of complete global brain ischemia: two-phase damage of Purkinje cells and hippocampal CA1 pyramidal cells

1990 ◽  
Vol 80 (5) ◽  
pp. 527-534 ◽  
Author(s):  
M. Sato ◽  
H. Hashimoto ◽  
F. Kosaka
Keyword(s):  
Purkinje Cells ◽  
Brain Ischemia ◽  
Neuronal Damage ◽  
Pyramidal Cells ◽  
Two Phase ◽  
Global Brain Ischemia ◽  
Histological Changes ◽  
Ca1 Pyramidal Cells ◽  
Hippocampal Ca1 ◽  
Global Brain

Neuroprotection and Enhancement of Spatial Memory by Herbal Mixture HT008-1 in Rat Global Brain Ischemia Model

2008 ◽  
Vol 36 (02) ◽  
pp. 287-299 ◽  
Author(s):  
Yun Tai Kim ◽  
Youn-Ju Yi ◽  
Mi-Yeon Kim ◽  
Youngmin Bu ◽  
Zhen Hua Jin ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Brain Ischemia ◽  
Neuronal Damage ◽  
Memory Function ◽  
Neuronal Cell ◽  
Memory Deficit ◽  
Global Brain Ischemia ◽  
Herbal Mixture ◽  
Y Maze ◽  
Global Brain

To investigate whether HT008-1, a prescription used in traditional Korean medicine to treat mental and physical weakness, has a neuroprotective effect on a rat model of global brain ischemia and an enhancing effect against memory deficit following ischemia. Global brain ischemia was induced for 10 min by using 4-vessel occlusion (4-VO). HT008-1 was orally administered at doses of 30, 100, and 300 mg/kg respectively twice at 0 and 90 min after ischemia. The effect on memory deficit was investigated by using a Y-maze neurobehavioral test 4 days after brain ischemia, and the effect on neuronal damage was measured 7 days after ischemia. The mechanism of action was studied immunohistochemically using an anti-CD11b (OX-42) antibody. The oral administration of HT008-1 at 100 and 300 mg/kg significantly reduced hippocampal neuronal cell death by 49% and 53%, respectively, compared with a vehicle-treated group, and also improved spatial memory function in the Y-maze test. Immunohistochemically, HT008-1 inhibited OX-42 expression in the hippocampus. The effects of HT008-1 were more pronounced than those of its individual herb components. The herbal mixture HT008-1 protects the most vulnerable CA1 pyramidal cells of the hippocampus and enhances spatial memory function against global brain ischemia; an anti-inflammatory effect may be one of the mechanisms of action.

Abstract 2837: Delayed Calpain Inhibition Is Neuroprotective After Transient Global Brain Ischemia

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Zhaoming Chen ◽  
James R Frederick ◽  
Matthew B Bevers ◽  
Lori P Ingleton ◽  
Marek Ma ◽  
...  
Keyword(s):  
Brain Ischemia ◽  
Therapeutic Window ◽  
Calpain Inhibitor ◽  
Global Brain Ischemia ◽  
Treatment Groups ◽  
Pyramidal Layer ◽  
Hippocampal Ca1 ◽  
Bilateral Carotid ◽  
Calpain Inhibition ◽  
Global Brain

Introduction/Hypothesis: The delay in neurodegeneration after transient global brain ischemia offers a potentially broad therapeutic window for inhibiting molecular injury mechanisms. One such mechanism, calpain-mediated proteolysis, peaks between 24 and 72 hours after transient forebrain ischemia (TFI) in rats. This study tests the hypothesis that calpain inhibition is neuroprotective when initiated 22 hours after TFI. Methods: Male Long Evans rats (400 – 450 g) were anesthetized (halothane), mechanically ventilated, and instrumented for temperature and hemodynamic monitoring. Each underwent 10 minutes of TFI induced by reversible bilateral carotid occlusion and hypovolemic hypotension (MAP 30 mm Hg). Twenty-two hours after TFI, rats were block randomized (n=6/group) to receive either calpain inhibitor (CEP-3453 (Cephalon), 60 mg/kg IV bolus and 30 mg/kg IV infusion for 50 hours) or vehicle (normal saline IV bolus and infusion for 50 hours). Sham operated rats served as controls. Rats were euthanized 72 hours after injury and brains were processed for immunohistochemistry. Hippocampal CA1 sector calpain activity was analyzed by immunofluorescence using primary antibody that specifically detects calpain-cleaved alpha-spectrin (Ab38). Neurodegeneration was quantified by counting normal appearing Hoechst-stained neuronal nuclei in the hippocampal CA1 pyramidal layer. Ab38 immunofluorescence intensity and normal nuclei counts were compared between vehicle and CEP-3453 treatment groups using a two-tailed Student’s t-test (alpha error 0.05). Results: Baseline and post-injury hemodynamic parameters and temperature were not significantly different between vehicle and CEP-3453 treatment groups. Relative to sham operated controls, mean CA1 sector Ab38 immunofluorescence increased by 263 ± 281% in vehicle treated rats and 68 ± 147% in CEP-3453 treated rats (p=0.17). Normal CA1 pyramidal layer nuclei averaged 10 ± 12% of control in vehicle treated rats and 50 ± 42% of control in CEP-3453 treated rats (p=0.047). Conclusion: These results suggest a causal role for calpains in delayed post-ischemic neurodegeneration, and demonstrate a broad therapeutic window for calpain inhibition in this model of transient global brain ischemia.

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