Background: Stroke is the second leading cause of death and a major cause of disability of adults worldwide. Inflammatory processes are known to contribute to the pathophysiology of cerebral ischemia, especially following reperfusion. Chemokines and their receptors are involved in migration of leukocytes and have been implicated in the pathogenesis of ischemic stroke. Objective: In the present study, we investigated the effects of C-C chemokine receptor type 5 (CCR5) deficiency on neurological outcome, brain damage and expression of pro-inflammatory chemokines: chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (CC motif) ligand 3 (CCL3) and chemokine (C-C motif) ligand 5 (CCL5), and the brain-derived neurotrophic factor (BDNF). Methods: Adult male C57BL/6 (wild-type) (WT) and CCR5 deficient mice were subjected to transient cerebral ischemia induced by 25 min of bilateral common carotid artery occlusion (BCCAO) followed by 24 hours of reperfusion. Mice were divided into four groups: WT sham group, which underwent sham operation; WT ischemic group, which was subjected to transient bilateral common carotid artery occlusion, CCR5-/- sham group, which underwent sham operation, and CCR5-/- ischemic group, which was subjected to transient BCCAO. Results: In CCR5 deficiency, we observed a significant improvement in the neurological deficits associated with decreased brain infarcted area as evaluated by triphenyltetrazolium chloride (TTC). Moreover, CCR5 deficiency revealed decreased percentage of necrotic cavities areas and frequency of ischemic neurons by histometric analysis. In addition, CCR5-/- ischemic animals showed lower brain levels of the chemokine CXCL1 and higher levels of BDNF by ELISA, compared with WT BCCAo mice. Conclusion: Taken together, our results suggest a potential neuroprotection in the absence of CCR5 receptor during global brain ischemia and reperfusion injury.

Background: Alzheimer’s disease (AD) is the main cause of dementia worldwide. The definitive diagnosis of AD is clinicopathological and based on the identification of cerebral deposition of Amyloid β (Aβ) plaques and neurofibrillary tangles. However, the link between amyloid cascade and depositions of phosphorylated tau (p-tau) is still missing. In this scenario, inflammasomes might play a relevant role. Experimental models of AD have suggested that Aβ accumulation induces, through microglia, activation of the NLRP3 inflammasome. This activation contributes to the dissemination of Aβ and p-tau, as well as to hyperphosphorylation of tau. Also, in experimental models, NLPR1 promoted neuronal pyroptosis. There are neither comprehensive neuropathologic characterization nor clinicopathologic studies evaluating the NLRP1 and NLRP3 inflammasomes in subjects with AD. Objective: The current mini-review aims to summarize recent and promising findings on the role of NLRP1 and NLRP3 signaling in the pathophysiology of AD. We also sought to highlight the knowledge gap in patients with AD, mainly the lack of clinicopathologic studies on the interaction among inflammasomes, Aβ/tau pathology, and cognitive decline.