Neuroprotective effects of flavone luteolin in neuroinflammation and neurotrauma.

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 (COVID-19). 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, oxidative stress, neuroinflammation, and the severity of neuroinflammatory diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and TBI pathogenesis. In conclusion, luteolin can improve cognitive decline and enhance neuroprotection in neurodegenerative diseases, TBI, and stroke.

Traumatic Injury of Major Cerebral Venous Sinuses Associated with Traumatic Brain Injury or Head and Neck Trauma: Analysis of National Trauma Data Bank.

BACKGROUND: The natural history and epidemiological aspects of traumatic injury of major cerebral venous sinuses are not fully understood. We determined the prevalence of traumatic injury of major cerebral venous sinuses and impact on the outcome of patients with traumatic brain injury, and/or head and neck trauma. METHODS: All the patients who were admitted with traumatic brain injury or head and neck trauma were identified by ICD-9-CM codes from the National Trauma Data Bank (NTDB), using data files from 2009 to 2010. NTDB represents one of the largest trauma databases and contains data from over 900 trauma centers across the United States. Presence of thrombosis, intimal tear, or dissection (traumatic injury) of major cerebral venous sinuses was identified in these patients by using Abbreviated Injury Scale predot codes. Admission Glasgow Coma Scale (GCS) score, Injury Severity Score (ISS), In-hospital complications, and treatment outcome were compared between patients with and without traumatic injury of major cerebral venous sinuses. RESULTS: A total of 76 patients were identified with traumatic injury of major cerebral venous sinuses among 453,775 patients who had been admitted with head and neck trauma. The rate of penetrating injury was higher among patients with traumatic injury of major cerebral venous sinuses (11.8% versus 2.5%, p = 0.0001). The patients with traumatic injury of major cerebral venous sinuses had a significantly higher rate of intracranial hemorrhage in comparison to patients without traumatic injury of major cerebral venous sinuses. The odds of in-hospital mortality remained significantly higher for patients with traumatic injury of major cerebral venous sinuses after adjusting for age, gender, admission GCS score, ISS injury type, and presence of intracranial hemorrhage [odds ratio (OR): 6.929; 95% confidence interval (CI) 1.337-35.96; p < 0.020]. The odds of discharge to nursing home remained higher for patients with traumatic injury of major cerebral venous sinuses after adjusting for potential confounders (OR: 1.8401; 95% CI 1.18-2.85, p < 0.0065). CONCLUSION: Although infrequent, traumatic injury of major cerebral venous sinuses in head and neck trauma is associated with higher rates of in-hospital mortality and discharge to a nursing home.

Paradoxical cerebral air embolism causing large vessel occlusion treated with endovascular aspiration.

Cerebral air embolism is a dreaded complication of invasive medical procedures. The mainstay of therapy for patients with cerebral air embolism has been hyperbaric oxygen therapy, high flow oxygen therapy, and anticonvulsants. We present a novel therapeutic approach for treatment of cerebral air embolism causing large vessel occlusion, using endovascular aspiration. Our patient developed a cerebral air embolism following sclerotherapy for varicose veins. This caused near total occlusion of the superior division of the M2 segment of the right middle cerebral artery. Symptoms included unilateral paralysis, unintelligible speech, and hemianopia; National Institutes of Health Stroke Scale (NIHSS) on presentation was 16. The air embolism was treated using a distal aspiration technique. Angiography following aspiration showed Thrombolysis in Cerebral Infarction 2B reperfusion. Following aspiration, the patient was re-examined; NIHSS at that time was 4. At 1 month follow-up, the modified Rankin Scale score was 1 and NIHSS was 1. Treatment of cerebral air embolism is discussed.

Paradoxical cerebral air embolism causing large vessel occlusion treated with endovascular aspiration.

Cerebral air embolism is a dreaded complication of invasive medical procedures. The mainstay of therapy for patients with cerebral air embolism has been hyperbaric oxygen therapy, high flow oxygen therapy, and anticonvulsants. We present a novel therapeutic approach for treatment of cerebral air embolism causing large vessel occlusion, using endovascular aspiration. Our patient developed a cerebral air embolism following sclerotherapy for varicose veins. This caused near total occlusion of the superior division of the M2 segment of the right middle cerebral artery. Symptoms included unilateral paralysis, unintelligible speech, and hemianopia; National Institutes of Health Stroke Scale (NIHSS) on presentation was 16. The air embolism was treated using a distal aspiration technique. Angiography following aspiration showed Thrombolysis in Cerebral Infarction 2B reperfusion. Following aspiration, the patient was re-examined; NIHSS at that time was 4. At 1 month follow-up, the modified Rankin Scale score was 1 and NIHSS was 1. Treatment of cerebral air embolism is discussed.

What is the right temperature to cool post-cardiac arrest patients?

CITATION: Niklas Nielsen, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, Pellis T, Stammet P, Wanscher M, Wise MP, Åneman A, Al-Subaie N, Boesgaard S, Bro-Jeppesen J, Brunetti I, Bugge JF, Hingston CD, Juffermans NP, Koopmans M, Køber L, Langørgen J, Lilja G, Møller JE, Rundgren M, Rylander C, Smid O, Werer C, Winkel P, Friberg H. Targeted temperature management at 33 °C versus 36 °C after cardiac arrest. N Engl J Med. 2013;369:2197-206. doi: 10.1056/NEJMoa1310519 . Epub 2013 Nov 17. Pub Med PMID: 20089970. BACKGROUND: Brain ischemia and reperfusion injury leading to tissue degeneration and loss of neurological function following return of spontaneous circulation after cardiac arrest (CA) is a well-known entity. Two landmark trials in 2002 showed improved survival and neurological outcome of comatose survivors of out-of-hospital cardiac arrest (OHCA) of presumed cardiac origin when the patients were subjected to therapeutic hypothermia of 32 to 34 °C for 12 to 24 hours. However, the optimal target temperature for these cohorts is yet to be established and also it is not clear whether strict fever management and maintaining near normal body temperature are alone sufficient to improve the outcome. OBJECTIVE: The objective is to determine whether a hypothermic goal of a near-normal body temperature of 36 °C reduces all-cause mortality compared with a moderate hypothermia of 33 °C for the unconscious survivors of OHCA of presumed cardiac origin when subjected randomly to these different targeted temperatures. DESIGN: A multicenter, international, open label, randomized controlled trial. SETTING: Thirty-six ICUs in Europe and Australia participated in this study. PARTICIPANTS: Unconscious adults (older than 18 years of age) who survived (Glasgow coma scale less than 8) OHCA due to presumed cardiac origin with subsequent persistent return of spontaneous circulation (more than 20 minutes without chest compressions). INTERVENTION: The above participant cohorts were randomized to targeted body temperature of either 33 °C or 36 °C for 36 hours after the CA with gradual rewarming of both groups to 37 °C (hourly increments of 0.5 °C) after the initial 28 hours. Body temperatures in both the groups were then maintained below 37.5 °C for 72 hours after the initial 36 hours. OUTCOMES: Primary outcome measure of all-cause mortality in both the groups at the end of the trial with the secondary outcome measure of all-cause mortality, composite neurological function as evaluated by cerebral performance category scale and modified ranking scale at the end of 180 days were studied. RESULTS: Out of the 939 participants, all-cause mortality at the end of the trial was 50 % in the 33 °C group (225 of 466 patients) compared with 48 % in the 36 °C group (235 of 473 patients); the hazard ratio with a temperature of 33 °C was 1.06 (95 % confidence interval (CI) 0.89 to 1.28, P = 0.51). At the end of 180 days, 54 % of patients in the 33 °C group versus 52 % in the 36 °C group had died or had poor neurological outcome according to cerebral performance category (risk ratio 1.02, 95 % CI 0.88 to 1.16, P = 0.78) but the modified ranking scale at the end of 180 days was unchanged (52 %) in both groups (risk ratio 1.01, 95 % CI 0.89 to 1.14, P = 0.87). CONCLUSIONS: Maintaining targeted lower normothermia of 36 °C had similar outcomes compared with induced moderate hypothermia of 33 °C for unconscious survivors of OHCA of presumed cardiac cause.