Interaction between a rat model of cerebral ischemia and β-amyloid toxicity: Inflammatory responses

• Published in: Stroke (1970) 2005, Vol.36 (1), p.107-112
• Main Authors: WHITEHEAD, Shawn N, HACHINSKI, Vladimir C, CECHETTO, David F
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - chemically induced; Alzheimer Disease - etiology; Alzheimer Disease - pathology; Amyloid beta-Peptides - administration & dosage; Animals; Behavior, Animal; Biological and medical sciences; Brain - pathology; Brain Chemistry; Brain Ischemia - chemically induced; Brain Ischemia - complications; Coloring Agents; Congo Red; Disease Models, Animal; Encephalitis - chemically induced; Encephalitis - complications; Endothelins - administration & dosage; Gliosis - chemically induced; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Immunohistochemistry; Injections; Learning; Male; Medical sciences; Motor Skills; Nervous system (semeiology, syndromes); Neurology; Neuropharmacology; Neuroprotective agent; Peptide Fragments - administration & dosage; Pharmacology. Drug treatments; Rats; Rats, Wistar; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/01.STR.0000149627.30763.f9

Clinical data suggest that Alzheimer disease (AD) and stroke together potentiate cognitive impairment. Inflammatory mechanisms are involved in AD pathology and stroke and may be the mediator between AD and stroke toxicity. AD was modeled by cerebroventricular injections of beta-amyloid (Abeta[25-35]) and subcortical lacunar infarcts by striatal endothelin injections. Inflammatory mechanisms were examined using immunohistochemical analysis. Memory and motor tasks were assessed using the Montoya staircase test. Abeta injections elicited increases in pathological and inflammatory correlates of AD in multiple forebrain sites. Increases in astrocytosis and reactive microglia in the hippocampus were enhanced with the combination of endothelin and Abeta(25-35). Abeta(25-35) treatment decreased performance in the Montoya staircase behavioral test. The enhanced inflammatory response with Abeta toxicity and ischemia may mediate the inability to improve behavioral performance caused by the stroke. Anti-inflammatory treatment may ameliorate the pathological and behavioral deficits associated with the combination of AD and stroke.