Do dendritic spines contribute to ischemic tolerance?

Abstract

Global ischemia destroys the CA1 pyramidal cells of the hippocampus. This cell loss can be prevented by ischemic preconditioning (IP). IP is a phenomenon whereby brief episodes of ischemia protect against a later more severe insult. Dendritic spines have been suggested to be neuroprotective by regulating toxic calcium levels independently of the parent dendrite. Therefore, dendritic spine formation may play a role in the development of IP. The purpose of the present experiment was to examine the effects of IP on spine densities in the CA1 region in gerbils. Animals received bilateral carotid occlusions of 1.5 min (pre-conditioning) and 5 min (ischemic preconditioning) in duration. Spine densities were calculated from apical and basilar dendrites of CA1 pyramidal cells in ischemic preconditioned animals that survived 3 (IP3), 10 (IP 10) or 30 (IP30) days, preconditioned only (PO) animals, and sham animals. Animals were tested on the same days for habituation to a novel open field. Sections were stained using a modified Golgi-Cox procedure and spines were visualized using a Neurolucida® neuron tracing system. Results show that PO, IP 10 and IP30 animals have significantly higher spine densities on basilar, proximal and terminal dendrites than all other groups of animals. In the open field, IP animals initially displayed habituation impairments that recovered with time. This apparent recovery coincided with the increase in CA1 spine density. These data may reflect a role for dendritic spines in the neuroprotection and recovery of function associated with ischemic tolerance.