Affiliations: Max-Planck-Institute for Neurological Research, Department of Experimental Neurology, Cologne, Germany
Note: [] Address correspondence and reprints requests to: Dr. Dirk
Hermann, Max-Planck-Institute for Neurological Research, Department of
Experimental Neurology, Gleueler Str. 50, D-50931 Cologne, Germany; Tel.:
+49-221-4726-217; Fax: +49-221-4726-298; E-mail: [email protected]
Abstract: The effects of spreading depression-like DC depolarizations on
biochemical changes and gene expression were examined following trau-matic
neocortical lesions, as induced by transcranial cold injury. The surrounding of
traumatic cold lesions was characterized by increased glu-cose and lactate
contents, without major disturbances of protein synthesis or energy state. A
transient pH decrease by 0.4 units was noticed 1 h post-injury, which shifted
towards alkaline values by 3 h. These changes were similar in animals with
spontaneous spreading depression-like DC shifts (n = 14) and those without
spreading depressions (n = 7), but there was a marked difference in the gene
response. In injured animals without SD, only a short-lasting response of
c-fos, junB, c-jun and MKP-1 mRNAs as well as c-Fos protein was bilaterally
found in the piri-form cortex, and - with ipsilateral dominance - the
dentate gyrus and hippocampal CA3/4 fields at 1 h after lesioning. In injure d
animals with spreading depressions, on the contrary, a strong elevation was
seen in layers II-IV and VI of the injury-remote ipsilateral cerebral
cortex, which persisted over as long as 6 h. The expression of c-fos, 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 after
transient DC shifts, and decreased thereafter mono-exponentially 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-related
gene response, but - in contrast to focal ischemia - it does not
aggravate the metabolic dysfunction.
