Kaiser Sandra, Fritsch Anna, Jakob Lena, Schallner Nils
Department of Anesthesiology & Critical Care, Medical Center-University of Freiburg, Freiburg, Germany.
Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Eur J Neurosci. 2025 Jan;61(2):e16666. doi: 10.1111/ejn.16666.
Traumatic brain injury is one of the most common cerebral incidences worldwide. Repetitive mild traumatic brain injuries occurring, for example, in athletes or victims of abuse, can cause chronic neurodegeneration due to neuroinflammation, in which the crosstalk between reactive astrocytes and activated microglia is crucial for modulating neuronal damage. The inducible enzyme heme oxygenase-1 and its product carbon monoxide are known to be ascribed neuroprotective and anti-inflammatory properties. We caused repetitive mild traumatic brain injuries in wild-type mice compared to mice without microglial heme oxygenase-1 expression. Additionally, mice were treated daily with either air or carbon monoxide exogenously. In wild-type mice, we observed enhanced microglia activation and astrogliosis as well as vasodilation after repetitive trauma. In heme oxygenase-1 knockout mice, we observed enhanced activation of microglia and astrocytes at baseline pretrauma with a lack of an adequate inflammatory response to repetitive injury. However, the knockout led to enhanced NF-κB and IFNγ expression in the post-trauma period. Carbon monoxide exerted neuroprotection, as suggested by reduced wake-up times in mice and by beneficially altering inflammation post-traumatic brain injury. This study further underlines the crucial role of the heme oxygenase-1/carbon monoxide system in the modulation of neuronal damage and the associated neuroinflammatory response after repetitive traumatic brain injury.
创伤性脑损伤是全球最常见的脑部疾病之一。例如，在运动员或受虐受害者中发生的重复性轻度创伤性脑损伤，可因神经炎症导致慢性神经退行性变，其中反应性星形胶质细胞和活化小胶质细胞之间的相互作用对于调节神经元损伤至关重要。已知诱导型酶血红素加氧酶-1及其产物一氧化碳具有神经保护和抗炎特性。与无微胶质细胞血红素加氧酶-1表达的小鼠相比，我们在野生型小鼠中造成重复性轻度创伤性脑损伤。此外，每天给小鼠外源性吸入空气或一氧化碳进行治疗。在野生型小鼠中，我们观察到重复性创伤后小胶质细胞活化增强、星形胶质细胞增生以及血管舒张。在血红素加氧酶-1基因敲除小鼠中，我们观察到创伤前基线时小胶质细胞和星形胶质细胞的活化增强，但对重复性损伤缺乏充分的炎症反应。然而，基因敲除导致创伤后时期NF-κB和IFNγ表达增强。一氧化碳发挥了神经保护作用，这表现在小鼠苏醒时间缩短以及创伤性脑损伤后炎症得到有益改变。这项研究进一步强调了血红素加氧酶-1/一氧化碳系统在调节重复性创伤性脑损伤后神经元损伤及相关神经炎症反应中的关键作用。
