Neuroprotective role of ornithine decarboxylase activation in transient focal cerebral ischaemia:: a study using ornithine decarboxylase-overexpressing transgenic rats

Nuclear magnetic resonance imaging (MRI) was used to study dynamics of maturation and the size of ischaemic stroke lesions in rats with greatly increased activity of ornithine decarboxylase (ODC). Syngenic rats, either with or without chronic pre-ischaemic treatment with an ODC inhibitor, alpha-difluoromethylornithine (DFMO), as well as ODC-overexpressing transgenic rats were subjected either to transient middle cerebral artery (MCA) occlusion or permanent occlusion of the cortical branch of MCA. The two models were chosen to assess the role of ODC activity in damage caused by ischaemia and reperfusion, respectively. Diffusion of water was quantified by means of the trace of the diffusion tensor (D-av = 1/3TraceD) to assess the extent of energy failure and cytotoxic oedema, whereas the spin-spin relaxation time (T-2) was used as a quantitative indicator of irreversible damage by MRI. Exposure to transient MCA occlusion resulted in significantly smaller stroke lesions in the ODC-overexpressing transgenic (246 +/- 14 mm(3)) than in syngenic (320 +/- 9 mm(3)) or DFMO-treated (442 +/- 63 mm(3)) rats as determined 48 h after the occlusion. The differences in sizes were due to smaller lesions in the cortical tissue (transgenic vs, syngenic) or both in cortical and striatal regions (transgenic vs. DFMO-treated animals), The degree of irreversible oedema was greater in DFMO-treated rats than in syngenic or transgenic animals indicating accelerated development of a permanent damage in the absence of ODC induction. Cortical infarct following permanent MCA occlusion developed faster in the DFMO-treated than in syngenic or transgenic rats as the lesion sizes at 10 h were 26.2 +/- 4.3 mm(3), 14.2 +/- 2.3 mm(3) and 12.3 +/- 1.9 mm(3), respectively. However, the stroke volumes by 48 h were not statistically different in the three animal groups. The present data demonstrate that ODC activation is an endogenous neuroprotective measure in transient cerebral ischaemia.