Investigation of the neuroprotective effects of clomethiazole and minocycline in an adult mouse model of hypoxia-ischemia.

摘要

Each year there are approximately 16,000 deaths in Canada from stroke related injury. With the aging of the ‘baby boomers’ the number of strokes will increase over the next decade. These facts emphasize the importance of stroke prevention and the discovery of new methods of stroke treatment.; In this study, a Rice-Vannucci model of cerebral ischemia was established in the adult mouse and immunohistological markers of cellular injury were used to determine areas of damage. The location and extent of brain injuries observed in the present study are consistent with prior studies. Damage was found in the hippocampus, striatum and cortex of the ipsilateral hemisphere. This study has, however, demonstrated a great degree of variability among animals.; Expression of activated microglia, as determined by OX-42 immunoreactivity, in general did not occur until 24 hours post hypoxia-ischemia. Vimentin-positive cells were found at all time points following hypoxia-ischemia with a tendency for increased expression on the contralateral hemisphere. Expression of the cell stress marker Hsp70 occurred at 12 hours post hypoxia-ischemia in the hippocampal region of the ipsilateral hemisphere.; This HI model was then used to assess the neuroprotective actions of two pharmacological agents, clomethiazole and minocycline. Quantitative analysis of infarct volume was performed by using TTC to stain fresh brain tissue samples combined with solvent extraction and spectrophotometery. The present study found that neither clomethiazole-treated nor minocycline-treated animals were significantly different, in terms of infarct volume, from vehicle-treated and animals that received hypoxia-ischemia alone. Clomethiazole administration resulted in a dramatic decline in rectal temperature when compared with vehicle administration. Interestingly, although clomethiazole produced hypothermia, which is considered a ‘gold standard’ in stroke treatment, it did not provide neuroprotection in this model.