Neuroinflammation leads to neurodegeneration, cognitive defects, and neurodegenerative disorders. Neurotrauma/traumatic brain injury (TBI) can cause activation of glial cells, neurons, and neuroimmune cells in the brain to release neuroinflammatory mediators. Neurotrauma leads to immediate primary brain damage (direct damage), neuroinflammatory responses, neuroinflammation, and late secondary brain damage (indirect) through neuroinflammatory mechanism. Secondary brain damage leads to chronic inflammation and the onset and progression of neurodegenerative diseases. Currently, there are no effective and specific therapeutic options to treat these brain damages or neurodegenerative diseases. Flavone luteolin is an important natural polyphenol present in several plants that show anti-inflammatory, antioxidant, anticancer, cytoprotective, and macrophage polarization effects. In this short review article, we have reviewed the neuroprotective effects of luteolin in neurotrauma and neurodegenerative disorders and pathways involved in this mechanism. We have collected data for this study from publications in the PubMed using the keywords luteolin and mast cells, neuroinflammation, neurodegenerative diseases, and TBI. Recent reports suggest that luteolin suppresses systemic and neuroinflammatory responses in Coronavirus disease 2019 . Studies have shown that luteolin exhibits neuroprotective effects through various mechanisms, including suppressing immune cell activation, such as mast cells, and inflammatory mediators released from these cells. In addition, luteolin can suppress neuroinflammatory response, activation of microglia and astrocytes,

Background To identify whether the risk of intracerebral hemorrhage is higher in patients with coronavirus disease 2019 (COVID-19), we compared the risk factors, comorbidities, and outcomes in patients intracerebral hemorrhage and COVID-19 and those without COVID-19. Methods We analyzed the data from the Cerner deidentified COVID-19 data set derived from 62 health care facilities. The data set included patients with an emergency department or inpatient encounter with discharge diagnoses codes that could be associated with suspicion of or exposure to COVID-19 or confirmed COVID-19. Results There were a total of 154 (0.2%) and 667 (0.3%) patients with intracerebral hemorrhage among 85,645 patients with COVID-19 and 197,073 patients without COVID-19, respectively. In the multivariate model, there was a lower risk of intracerebral hemorrhage in patients with COVID-19 (odds ratio 0.5; 95% confidence interval 0.5–0.6; p < .0001) after adjustment for sex, age strata, race/ethnicity, hypertension, diabetes mellitus, nicotine dependence/tobacco use, hyperlipidemia, atrial fibrillation, congestive heart failure, long-term anticoagulant use, and alcohol abuse. The proportions of patients who developed pneumonia (58.4% versus 22.5%; p < .0001), acute kidney injury (48.7% versus 31.0%; p < .0001), acute myocardial infarction (11% versus 6.4%; p = .048), sepsis (41.6% versus 22.5%; p < .0001), and respiratory failure (61.7% versus 42.3%; p < .0001) were significantly higher among patients with intracerebral hemorrhage and COVID-19 compared with those without COVID-19. The in-hospital mortality among patients with intracerebral hemorrhage and COVID-19 was significantly higher compared with that among those without COVID-19 (40.3% versus 19.0%; p < .0001). Conclusions Our analysis does not suggest that rates of intracerebral hemorrhage are higher in patients with COVID-19. The higher mortality in patients with intracerebral hemorrhage and COVID-19 compared with those without COVID-19 is likely mediated by higher frequency of comorbidities and adverse in-hospital events. Supplementary Information The online version contains supplementary material available at 10.1007/s12028-021-01297-y.

Objectives: Acute ischemic stroke patients are at risk of acute kidney injury due to volume depletion, contrast exposure, and preexisting comorbid diseases. We determined the occurrence rate and identified predictors associated with acute kidney injury in acute ischemic stroke patients. Setting: Multiple specialized ICUs within academic medical centers. Design: Post hoc analysis of pooled data from prospective randomized clinical trials. Patients: Acute ischemic stroke patients recruited within 3 hours or within 5 hours of symptom onset. Interventions: IV recombinant tissue plasminogen activator, endovascular treatment, IV albumin, or placebo. Measurements and Main Results: Serum creatinine levels from baseline and within day 5 or discharge were used to classify acute kidney injury classification into stages. Any increase in serum creatinine was seen in 697 (36.1%) and acute kidney injury was seen in 68 (3.5%) of 1,931 patients with acute ischemic stroke. Severity of acute kidney injury was grade I, II, and III in 3.1%, 0.4%, and 0.05% patients, respectively. Patients with albumin (5.5% compared with 2.6%; p = 0.001), preexisting hypertension (4.3% compared with 1.5%; p = 0.0041), and preexisting renal disease (9.1% compared with 3.0%; p < 0.0001) had higher risk of acute kidney injury. The risk of acute kidney injury was lower between those who either underwent CT angiography (2.0% compared with 4.7%; p = 0.0017) or endovascular treatment (1.6% compared with 4.2%; p = 0.0071). In the multivariate analysis, hypertension (odds ratio, 2.6; 95% CI, 1.2–5.6) and renal disease (odds ratio, 3.5; 95% CI, 1.9–6.5) were associated with acute kidney injury. The risk of death was significantly higher among patients with acute kidney injury (odds ratio, 2.7; 95% CI, 1.4–4.9) after adjusting for age and National Institutes of Health Stroke Scale score strata. Conclusions: The occurrence rate of acute kidney injury in acute ischemic stroke patients was low and was not higher in patients who underwent CT angiogram or those who received endovascular treatment. Occurrence of acute kidney injury increased the risk of death within 3 months among acute ischemic stroke patients.

Acute traumatic brain injury (TBI) leads to neuroinflammation, neurodegeneration, cognitive decline, psychological disorders, increased blood-brain barrier (BBB) permeability, and microvascular damage in the brain. Inflammatory mediators secreted from activated glial cells, neurons, and mast cells are implicated in the pathogenesis of TBI through secondary brain damage. Abnormalities or damage to the neurovascular unit is the indication of secondary injuries in the brain after TBI. However, the precise mechanisms of molecular and ultrastructural neurovascular alterations involved in the pathogenesis of acute TBI are not yet clearly understood. Moreover, currently, there are no precision-targeted effective treatment options to prevent the sequelae of TBI. In this study, mice were subjected to closed head weight-drop-induced acute TBI and evaluated neuroinflammatory and neurovascular alterations in the brain by immunofluorescence staining or quantitation by enzyme-linked immunosorbent assay (ELISA) procedure. Mast cell stabilizer drug cromolyn was administered to inhibit the neuroinflammatory response of TBI. Results indicate decreased level of pericyte marker platelet-derived growth factor receptor-beta (PDGFR-β) and BBB-associated tight junction proteins junctional adhesion molecule-A (JAM-A) and zonula occludens-1 (ZO-1) in the brains 7 days after weight-drop-induced acute TBI as compared with the brains from sham control mice indicating acute TBI-associated BBB/ tight junction protein disruption. Further, the administration of cromolyn drug significantly inhibited acute TBI-associated decrease of PDGFR-β, JAM-A, and ZO-1 in the brain. These findings suggest that acute TBI causes BBB/tight junction damage and that cromolyn administration could protect this acute TBI-induced brain damage as well as its long-time consequences.