Metabolic Disturbances and Gene Responses Following Cortical Injury in Rats: Relationship to Spreading Depression

Abstract

The effects of a cortex lesion on alterations in cortical direct-current (DC) potential, cerebral metabolism and gene expression were examined in rats at 1–6 h after transcranial cold injury. In 14 of 21 injured rats, spreading depression (SD)-like depolarizations were recorded, which were accompanied by a transient decrease in electroencephalogram activity and a parallel increase in perfusion. Metabolic disturbances did not differ between injured animals with and without SD. The lesion surrounding was characterized by increased glucose and lactate contents without major disturbances of protein synthesis or energy state. A transient peri-focal decrease in tissue pH by 0.4 units was noticed after 1 h, followed by tissue alkalosis 3 h post-injury. In injured animals without SD, a short-lasting expression of immediate-early gene (IEG) mRNAs was found in piriform cortex, in the dentate gyrus and hippocampal CA3/CA4 subfields at 1 h after lesioning. In injured animals with SDs, a strong elevation of IEGs was seen additionally in layers II-IV and VI of the injury-remote ipsilateral cerebral cortex, which persisted for as long as 6 h. The mRNA levels for c-fos, junB and mitogen-activated protein kinase phosphatase (MKP)-1 were closely related to the time interval between the last DC deflection and the termination of the experiment, yielding a post-depolarization decline with half-lives of 48, 75, and 58 min for c-fos, junB and MKP-1, respectively. The results of the present study demonstrate that SD is a prominent factor influencing trauma-related gene responses in the lesion-remote cerebral cortex. In contrast to focal cerebral ischemia, however, SDs do not aggravate the metabolic dysfunction in the area surrounding the lesion.