Long-Term Effects of Sequential Small Cortical Infarcts on Brain Volume and Cognitive Function

Multiple ischemic brain lesions are commonly associated with progressive cognitive impairment leading to some types of vascular dementia in the elderly. Only little is known about the underlying pathophysiological mechanisms. We here analyzed the effects of single and multiple small cortical infarcts on brain volume and cognitive function using the photothrombosis model in rats. Different experimental groups received single small infarcts in the forelimb somatosensory cortex (SL) or two sequential infarcts either immediately (DL0), 2 days (DL2), 7d (DL7), or 10 days (DL10) after the first infarct in the same area of the contralateral hemisphere. Compared to the animals with unilateral lesions (SL), brain volumetry performed 1 month after the second lesion revealed a global reduction in brain volume of 2.2–8.0% (excluding the lesioned area) in all groups with sequential infarcts. In a further study sham-operated as well as SL and DL2 animals were tested in a Morris water maze 2 months after the lesions. While SL animals showed no cognitive impairment in acquisition and probe trial tests compared with controls, DL2 animals revealed a slight but significant memory deficit, although there was no difference in swim speed between these groups. The present findings demonstrate a general loss of brain volume associated with cognitive deficits following sequential cortical infarcts, probably providing an animal model for the investigation of degenerative processes leading to vascular dementia.