Patients treated for aneurysmal subarachnoid hemorrhage show, in the long-term follow up, an elevated rate of cognitive disturbances that are mainly related to the impact of the initial bleeding: the neurotoxic effects of blood deposition in subarachnoidal spaces may result in a diffuse encephalopathy, but the intrinsic mechanism and the biochemical correlates are not known. In the present study we have evaluated mitochondrial function after experimental induction of subarachnoid hemorrhage. Mitochondrial function was evaluated in four different rat brain areas (frontal cortex, occipital cortex, hippocampus, and brain stem) after experimental isobaric subarachnoid hemorrhage in rats. Subarachnoid hemorrhage was induced by injecting 0.07 mL of arterial autologous blood into the cisterna magna. Intracranial pressure did not significantly increase. The nonsynaptic mitochondrial fraction was isolated from different rat brain areas, and the maximal rate of enzymatic reactions of some key enzymatic activities related to the Krebs cycle [nicotinamide adenine dinucleotide (oxidized form) (NAD+)-isocitrate dehydrogenase, citrate synthase, and succinate dehydrogenase] and of the electron transfer chain (cytochrome oxidase) were evaluated. The nonsynaptic mitochondrial fraction was utilized also to check parameters related to the mitochondrial respiration: state 3, state 4, uncoupled state, respiratory control ratio, and adenosine 5′-diphosphate/oxygen ratio. The biochemical parameters were measured at 1 and 72 hours after the subarachnoidal injection of blood. Subarachnoid hemorrhage did not affect the mitochondrial enzymatic activities both at 1 and 72 hours, while the mitochondrial respiration parameters were significantly affected: in particular, a significant decrease of respiratory control ratio in all tested brain areas was demonstrated. The increased mitochondrial vulnerability in the delayed phases could be one of the biochemical correlates of posthemorrhagic encephalopathy.
- Enzymatic activities
- Experimental subarachnoid hemorrhage
ASJC Scopus subject areas
- Clinical Neurology