Inflammation and Oxidative Stress: Potential Targets for Improving Prognosis After Subarachnoid Hemorrhage

Abstract

Subarachnoid hemorrhage (SAH) has a high mortality rate and causes long-term disability in many patients, often associated with cognitive impairment. However, the pathogenesis of delayed brain dysfunction after SAH is not fully understood. A growing body of evidence suggests that neuroinflammation and oxidative stress play a negative role in neurofunctional deficits. Red blood cells and hemoglobin, immune cells, proinflammatory cytokines, and peroxidases are directly or indirectly involved in the regulation of neuroinflammation and oxidative stress in the central nervous system after SAH. This review explores the role of various cellular and acellular components in secondary inflammation and oxidative stress after SAH, and aims to provide new ideas for clinical treatment to improve the prognosis of SAH.

Clinical Value of Inflammatory Cytokines in Patients with Aneurysmal Subarachnoid Hemorrhage

“…Although a mild inflammation is thought to aid in injury repair, excessive inflammation can aggravate brain edema, mitochondrial dysfunction, disruption of the blood-brain barrier (BBB), and neuronal apoptosis, all of which cause the further impairment of consciousness and are believed to contribute to the poor prognosis of patients with aSAH. 15 , 16 In addition, inflammation activation also occurs in the peripheral immune system. 17 Immune cell activation in the peripheral blood after aSAH is influenced by the sympathetic nervous system and the hypothalamic-pituitary-adrenal regulation.…”

Mesenchymal stem cells-derived therapies for subarachnoid hemorrhage in preclinical rodent models: a meta-analysis

“…Notably, the high-grade cerebral edema in early stage is identified to be an independent predictor of DCI and unfavorable clinical outcome [ 8 ]. Mechanically, inflammatory activity, oxidative stress, and apoptosis are throughout the entire course of SAH [ 9 , 10 ].…”

Angiotensin-(1–7) as a Potential Therapeutic Strategy for Delayed Cerebral Ischemia in Subarachnoid Hemorrhage

“…Blood extravasation after SAH leads to the exposure of the cerebral tissue to numerous intravascular components, triggering a local inflammatory response ( 13 ). This response is further aggravated by the accumulation of free radicals caused by the degradation of cellular components of the clot ( 14 ), ultimately generating a self-promoting detrimental loop ( 15 ). Microvascular dysfunction and cortical spreading depolarization can also occur in these patients and contribute to the DCI pathogenesis ( 6 ).…”

“…Neuroinflammation has been proposed to contribute to the DCI and poor outcome in SAH patients ( 15 ). RAS modulation either by inhibiting ACE/Ang-II/AT 1 R or stimulating the ACE2/Ang-(1–7)/MasR or AT 2 R axis has shown anti-neuroinflammatory effects in several brain pathologies ( Figure 2 ) but in vivo studies exploring the possibility of acting on RAS to improve SAH outcome are lacking and are needed in the future.…”

“…It has recently been proposed that inflammation and oxidative stress may be a common ground for most of the causes of DCI ( 6 , 15 ). After SAH blood components trigger an inflammatory response in the brain ( 13 ), that is further aggravated by the production of free radicals caused by the degradation of red blood cells from the clot ( 14 ); this builds up a self-promoting detrimental loop where neuroinflammation causes oxidative stress and oxidative stress aggravates neuroinflammation.…”