Effects of a mitochondrial calcium uniporter and P-selectin inhibitors on neural injury induced by global cerebral ischemia-reperfusion in male rats.

Abstract

Neural injury following ischemia-reperfusion (I/R) is induced by multiple pathophysiological pathways. This study aimed to use mitochondrial calcium channel and p-selectin inhibitors to weaken these pathways. One hundred and two rats were randomly divided into six groups. In the sham group, cerebral I/R induction and drug intervention were not performed. In the I/R group, cerebral I/R induction was induced. In the RR + FCN group, animals received only ruthenium red (RR) and fucoidan (FCN) intraperitoneally without I/R induction. In the I/R + RR group, animals received RR during the cerebral I/R period. In the I/R + FCN group, FCN was administered along with cerebral I/R. In the I/R +(RR + FCN) group, animals exposed to cerebral I/R received a combination of RR and FCN simultaneously. The shuttle box and new object tests were used to assess learning and memory. The superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) levels in the hippocampus were measured. Neuronal death in the hippocampal CA1 area was assessed via hematoxylin-eosin staining. FCN and RR significantly decreased the tissue MDA, IL-1β, TNF-α levels while increased the SOD level. These inhibitors significantly reduced learning disorders and cerebral edema following I/R. The rate of neuronal death was significantly lower in each of the receiving RR and FCN groups. This study revealed that the use of FCN and RR significantly attenuated the pathways associated with oxidative stress and inflammation as well as neuronal death following cerebral I/R, thereby reducing learning and memory impairments. The effects of neuroprotection were further determined when two inhibitors were used simultaneously. HIGHLIGHTS: Cerebral ischemia-reperfusion is associated with many neurological, sensory and motor defects. Multiple pathways of neural pathophysiology are activated during cerebral ischemia-reperfusion. The Administration of ruthenium and fucoidan weakens inflammatory pathways, oxidative stress, and learning dysfunctions caused by cerebral ischemia and reperfusion. Stronger Neuroprotective effects were observed during the simultaneous administration of ruthenium and fucoidan.