Response of distant regions affected by diaschisis commissuralis in one of the most common models of transient focal ischemia in rats

Abstract

Stroke induces widespread changes in the brain. In this paper, we monitored some markers of early (2 h) and delayed events (1, 3 and 7 days of reperfusion) initiated by middle cerebral artery occlusion in core/penumbra counterparts of the non-ischemic hemisphere (i.e. contra-core and contra-penumbra). Our results showed that a profound transient drop (2 h and 3 days) of protein synthesis was measured in the contra-core, while the contra-penumbra exhibited translation over-activity at the same time. Glutamate release was detected only in the contra-core, with a peak on the first day. Degenerating neurons became visible in the striatum (day 1), followed by cortex (day 3), earlier in contra-penumbra and later in contra-core. Moreover, the loss of NADPH diaphorase-positive neurons in the non-ischemic hemisphere was detected, with the greatest drop at the first day. Total microglia also started to fall, the earliest in the contra-penumbra region of the striatum (day 1), followed by the contra-core of the striatum and both cortex regions at the seventh day. In conclusion, transient focal ischemia affects remote regions of the brain and initiates processes involved in neuronal degeneration in an order which corresponds to the tissue sensitivity to ischemia, namely earlier in the contra-penumbra, and afterwards in the contra-core. The mechanism of secondary damage would influence the progressive neuronal loss of more distant brain regions.

Keywords: Contralateral hemisphere; Glutamate; Ischemia; Microglia; Middle cerebral artery occlusion; Neurodegeneration; Stroke.