Biochemical changes and gene expression following traumatic brain injury: Role of spreading depression

The effects of spreading depression-like DC depolarizations on biochemical changes and gene expression were examined following traumatic neocortical l esions, as induced by transcranial cold injury. The surrounding of traumati c cold lesions was characterized by increased glucose and lactate contents, without major disturbances of protein synthesis or energy state. A transie nt pH decrease by 0.4 units was noticed 1 h post-injury, which shifted towa rds alkaline values by 3 h. These changes were similar in animals with spon taneous spreading depression-like DC shifts (n = 14) and those without spre ading depressions (n = 7), but there was a marked difference in the gene re sponse. In injured animals without SD, only a short-lasting response of c-f os, junB, c-jun and MKP-1 mRNAs as well as c-Fos protein was bilaterally fo und in the piriform cortex, and - with ipsilateral dominance - the dentate gyrus and hippocampal CA3/4 fields at 1 h after lesioning. In injured anima ls with spreading depressions, on the contrary, a strong elevation was seen in layers II-IV and VI of the injury-remote ipsilateral cerebral cortex, w hich persisted over as long as 6 h. The expression of c-Sos, junB and MKP-1 mRNAs was closely related to the time interval between the last spreading depression and the end of the experiments. Levels were highest shortly afte r transient DC shifts, and decreased thereafter monoexponentially with half -lives of 48, 75 and 58 min for c-fos, junB and MKP-1 mRNAs, respectively. Thus, spreading depression is a prominent factor influencing the trauma-rel ated gene response, but - in contrast to focal ischemia - it does not aggra vate the metabolic dysfunction.