The new coronavirus has spread throughout the world in a very short time and now has become a pandemic. Most infected people have symptoms such as dry cough, dyspnea, tiredness, and fever. However, the Covid-19 infection disrupts various organs, including the liver, kidney, and nervous system. Common neurological symptoms of the Covid-19 infection include delirium, confusion, headache, and loss of sense of smell and taste. In rare cases it can cause stroke and epilepsy. The virus enters the nervous system either directly through nerve pathways or indirectly through the ACE2 receptor. The neurological symptoms of a Covid-19 infection in the brain are mainly due to either the entry of pro-inflammatory cytokines into the nervous system or the production of these cytokines by microglia and astrocytes. Pro-inflammatory cytokines can cause blood-brain barrier disruption, increase in glutamate and aspartate and reduce GABA levels, impairs the function of ion channels, and finally, high levels of cytokines can cause epilepsy. Understanding the potential mechanisms is necessary to gain better insight into COVID-19 induced seizure pathogenesis and to design the correct treatment strategies to achieve appropriate treatment for seizure and epilepsy.

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Nicotinamide phosphoribosyl transferase/pre-B cell colony-enhancing factor/visfatin (Nampt/PBEF/visfatin) is an adipocytokine. By synthesizing nicotinamide adenine dinucleotide (NAD(+)), Nampt/PBEF/visfatin functions to maintain an energy supply that has critical roles in cell survival. Cerebral ischemia leads to energy depletion and eventually neuronal death by apoptosis in specific brain regions specially the hippocampus. However, the role of Nampt/PBEF/visfatin in brain and cerebral ischemia remains to be investigated. This study investigated the role of administration Nampt/PBEF/visfatin in hippocampal CA3 area using a transient global cerebral ischemia model. Both common carotid arteries were occluded for 20 min followed by reperfusion. Saline as a vehicle and Nampt/PBEF/visfatin at a dose of 100 ng were injected intracerebroventricularly (ICV) at the time of cerebral reperfusion. To investigate the underlying mechanisms of Nampt/PBEF/visfatin neuroprotection, levels of expression of apoptosis-related proteins (caspase-3 activation, Bax protein levels, and Bcl-2 protein levels) 96 h after ischemia were determined by immunohistochemical staining. The number of active caspase-3-positive neurons in CA3 was significantly increased in the ischemia group, compared with the sham group (P < 0.001), and treatment with Nampt/PBEF/visfatin significantly reduced the ischemia/reperfusion-induced caspase-3 activation, compared to the ischemia group (P < 0.05). Also, results indicated a significant increase in Bax/Bcl-2 ratio in the ischemia group, compared with the sham group (P < 0.01). However, treatment with Nampt/PBEF/visfatin significantly attenuated the ischemia/reperfusion-induced increase in Bax/Bcl-2 ratio, compared with the ischemia group (P < 0.05). This study has indicated that Nampt/PBEF/visfatin entails neuroprotective effects against ischemia injury when used at the time of cerebral reperfusion. These neuroprotective mechanisms of Nampt/PBEF/visfatin occur through decrease the expression ofproapoptotic proteins (cleaved caspase-3 and Bax) and, on the other hand, increase the expression ofantiapoptotic proteins (Bcl-2). Thus, our findings indicate that Nampt/PBEF/visfatin is a new therapeutic target for cerebral ischemia.

Ischemia induces physiological alterations in neurons that lead to cell death. This study investigated the effects of pre-ischemic exercise on CA3 neurons. Rats were divided into three groups. Animals in the exercise group were trained 5 days a week for 4 weeks. Ischemia was induced by occlusion of both common carotid arteries (CCAs) for 20 min. Apoptotic cell death was detected by TUNEL assay. Furthermore, expression of different proteins was determined by immunohistochemical staining. The number of TUNEL-positive cells was significantly increased in the ischemia group, but pre-ischemic exercise significantly reduced apoptotic cell death (P < 0.001). In addition, our results showed a significant increase in the Bax/Bcl-2 ratio in the ischemia group. Pre-ischemic exercise attenuated this ratio (P < 0.05). Furthermore, the number of active caspase-3-positive neurons was significantly increased in the ischemia group, which was reduced markedly by exercise preconditioning (P < 0.05). This study showed that pre-ischemic exercise can exert neuroprotective effects against ischemia in CA3 neurons.

Oxidative stress is one of the pathological mechanisms responsible for the beta- amyloid cascade associated with Alzheimer's disease (AD). Previous studies have demonstrated the role of carnosic acid (CA), an effective antioxidant, in combating oxidative stress. A progressive cognitive decline is one of the hallmarks of AD. Thus, we attempted to determine whether the administration of CA protects against memory deficit caused by beta-amyloid toxicity in rats. Beta-amyloid (1–40) was injected by stereotaxic surgery into the Ca1 region of the hippocampus of rats in the Amyloid beta (Aβ) groups. CA was delivered intraperitoneally, before and after surgery in animals in the CA groups. Passive avoidance learning and spontaneous alternation behavior were evaluated using the shuttle box and the Y-maze, respectively. The degenerating hippocampal neurons were detected by fluoro-jade b staining. We observed that beta-amyloid (1–40) can induce neurodegeneration in the Ca1 region of the hippocampus by using fluoro-jade b staining. Also, the behavioral tests revealed that CA may recover the passive avoidance learning and spontaneous alternation behavior scores in the Aβ + CA group, in comparison with the Aβ group. We found that CA may ameliorate the spatial and learning memory deficits induced by the toxicity of beta-amyloid in the rat hippocampus.