Topiramate suppresses peri-infarct spreading depolarization and improves outcomes in a rat model of photothrombotic stroke.

Ischemic stroke can cause depolarized brain waves, termed peri-infarct depolarization (PID). Here, we evaluated whether topiramate, a neuroprotective drug used to treat epilepsy and alleviate migraine, has the potential to reduce PID. We employed a rat model of photothrombotic ischemia that can reliably and reproducibly induce PID and developed a combined electrocorticography-laser speckle contrast imaging (ECoG-LSCI) platform to monitor neuronal activity and cerebral blood flow (CBF) simultaneously. Topiramate administration after photothrombotic ischemia did not rescue CBF but significantly restored somatosensory evoked potentials in the forelimb area of the primary somatosensory cortex. Moreover, infarct volume was investigated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and neuronal survival was evaluated by Nissl staining. Mechanistically, the levels of inflammatory markers, such as ED1 (CD68), Iba-1, and GFAP, decreased significantly after topiramate administration, as did BDNF expression, while the expression of NeuN and Bcl-2/Bax increased, which is indicative of reduced inflammation and improved neuroprotection.

Investigating cerebral neurovascular responses to hyperglycemia in a rat model of type 2 diabetes using multimodal assessment techniques.

To study neurovascular function in type 2 diabetes mellitus (T2DM), we established a high-fat diet/streptozotocin (HFD/STZ) rat model. Electrocorticography-laser speckle contrast imaging (ECoG-LSCI) revealed that the somatosensory-evoked potential (SSEP) amplitude and blood perfusion volume were significantly lower in the HFD/STZ group. Cortical spreading depression (CSD) velocity was used as a measure of neurovascular function, and the results showed that the blood flow velocity and the number of CSD events were significantly lower in the HFD/STZ group. In addition, to compare changes during acute hyperglycemia and hyperglycemia, we used intraperitoneal injection (IPI) of glucose to induce transient hyperglycemia. The results showed that CSD velocity and blood flow were significantly reduced in the IPI group. The significant neurovascular changes observed in the brains of rats in the HFD/STZ group suggest that changes in neuronal apoptosis may play a role in altered glucose homeostasis in T2DM.

Revisiting the effects of exercise on cerebral neurovascular functions in rats using multimodal assessment techniques.

Physical activity in the form of aerobic exercise has many beneficial effects on brain function. Here, we aim to revisit the effects of exercise on brain morphology and neurovascular organization using a rat running model. Electrocorticography (ECoG) was integrated with laser speckle contrast imaging (LSCI) and applied to simultaneously detect CSD propagation and the corresponding neurovascular function. In addition, blood oxygenation level-dependent (BOLD) signal in fMRI was used to observe cerebral utilization of oxygen. Results showed significant decrease in somatosensory evoked potentials (SSEPs) and deceleration of CSD propagation in the EXE group. Western blot results in the EXE group showed significant increases in BDNF, GFAP, and NeuN levels and significant decreases in neurodegenerative disease markers. Decreases in SSEP and CSD parameters may result from exercise-induced increases in cerebrovascular system function and increases in the stability and buffering of extracellular ion concentrations and cortical excitability.