Persistent isoflurane-induced hypotension causes hippocampal neuronal damage in a rat model of chronic cerebral hypoperfusion

Postoperative cognitive dysfunction (POCD) is likely to occur in elderly people, who often suffer from cerebral hypoperfusion and white matter lesions even in the absence of cerebral infarctions.

Thirty-two adult male rats were randomly assigned to one of four groups: the cerebral normoperfusion + normotension group (n = 8), cerebral normoperfusion + hypotension group (n = 8), chronic cerebral hypoperfusion (CCH) + normotension group (n = 8), and CCH + hypotension group (n = 8). A rat model of CCH was developed via the permanent ligation of the bilateral common carotid arteries, but ligation was avoided in the cerebral normoperfusion groups. Two weeks later, the rats were intubated and mechanically ventilated under isoflurane anesthesia, and their mean arterial blood pressure was maintained over 80 mmHg (normotension) or below 60 mmHg (hypotension) for 2 h. After preparing brain slices, histological cresyl violet staining, ionized calcium binding adaptor molecule 1, a marker of microglial activation, or β amyloid precursor protein, a marker of axonal damage, were performed.

CCH per se caused microglial activation and axonal damage, which was not accentuated by hypotension. CCH alone did not cause neuronal damage, but CCH combined with hypotension caused significant neuronal damage in the hippocampal CA1 region. These results suggest that persistent hypotension during general anesthesia might cause neuronal damage in patients with CCH, such as elderly people, and contribute to prevention against POCD.