Neuroinflammation: friend and foe for ischemic stroke

Abstract

Stroke, the third leading cause of death and disability worldwide, is undergoing a change in perspective with the emergence of new ideas on neurodegeneration. The concept that stroke is a disorder solely of blood vessels has been expanded to include the effects of a detrimental interaction between glia, neurons, vascular cells, and matrix components, which is collectively referred to as the neurovascular unit. Following the acute stroke, the majority of which are ischemic, there is secondary neuroinflammation that both promotes further injury, resulting in cell death, but conversely plays a beneficial role, by promoting recovery. The proinflammatory signals from immune mediators rapidly activate resident cells and influence infiltration of a wide range of inflammatory cells (neutrophils, monocytes/macrophages, different subtypes of T cells, and other inflammatory cells) into the ischemic region exacerbating brain damage. In this review, we discuss how neuroinflammation has both beneficial as well as detrimental roles and recent therapeutic strategies to combat pathological responses. Here, we also focus on time-dependent entry of immune cells to the ischemic area and the impact of other pathological mediators, including oxidative stress, excitotoxicity, matrix metalloproteinases (MMPs), high-mobility group box 1 (HMGB1), arachidonic acid metabolites, mitogen-activated protein kinase (MAPK), and post-translational modifications that could potentially perpetuate ischemic brain damage after the acute injury. Understanding the time-dependent role of inflammatory factors could help in developing new diagnostic, prognostic, and therapeutic neuroprotective strategies for post-stroke inflammation.

TREM-2-p38 MAPK signaling regulates neuroinflammation during chronic cerebral hypoperfusion combined with diabetes mellitus

“…A number of signaling molecules, including mitogenactivated protein kinases (MAPKs) and triggering receptor expressed on myeloid cells 2 (TREM-2), are involved in the modulation of microglial activation and inflammatory responses [12,13]. Extracellular signal-regulated kinases 1 and 2 (ERK1/2), p38 MAPK, and c-Jun Nterminal kinases (JNK) are three major MAPKs, which regulate a wide variety of cellular processes and play an important role in regulating the expression of proinflammatory cytokines such as tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) [14]. TREM-2 is an important innate immune receptor uniquely expressed on the microglia and is involved in down-regulating neuroinflammation in the central nervous system (CNS) [15].…”

Post-Ischaemic Immunological Response in the Brain: Targeting Microglia in Ischaemic Stroke Therapy

“…However, the exact contributions of microglia in the context of ischaemic stroke are not yet fully understood. For example, it is unclear whether microglia can generate beneficial effects in both the acute and subacute post-ischaemic phases since neuroinflammation has roles in both promoting recovery and exacerbating secondary neuronal injury [21]. The complex and multiphasic roles displayed by microglia in ischaemic stroke pathophysiology constitute a major challenge to the development of immunomodulatory therapies.…”

Arginine is neuroprotective through suppressing HIF-1α/LDHA-mediated inflammatory response after cerebral ischemia/reperfusion injury

“…Stroke occurrence leads to high death rate and serious disability. Ischemia stroke accounts for 85% of different types of stroke [1]. After ischemic phase, the following reperfusion causes the secondary stage of injury, involving neuroinflammation, oxidative stress and bloodbrain-barrier break [2,3].…”