Brain Ischemia, and Reperfusion Injury: A Clinical and Physiological Investigation of Neuroinflammation and Chronic Neuroinflammatory Diseases Volume 53- Issue 4

Rajiv Kumar*

• University of Delhi, India

Received: October 25, 2023; Published: November 01, 2023

*Corresponding author: Rajiv Kumar, University of Delhi, New Delhi, 110007, India

DOI: 10.26717/BJSTR.2023.53.008423

Abstract PDF

Abbreviations: ROS: Reactive Oxygen Species; RNS: Reactive Nitrogen Species; BBB: Blood-Brain Barrier; IL: Interleukin; TNF: Tumor Necrosis Factor

The mechanistic concepts is a complex phenomenon of inflammation, brain ischemia, and reperfusion injury. Moreover, other complex unwanted cellular events is neuroinflammation and chronic neuroinflammatory diseases and disorders, including movement disorders, sensory disturbance, and higher brain dysfunction. These complications come into existence just because of ischemic stroke, which destroys neuronal circuits and induces the process of apoptosis of nerve cells. Meanwhile, cerebral oedema and inflammation initiated, after ischemic damage, these unwanted cellular events intensify prognosis and signs of stroke and later on, initiate tissue damages [1]. If the brain inflammation can be treated, then there are huge possibilities for recovery from ischemic stroke (Figure 1). Therefore, the author’s objective is to prepare a blueprint of such remedies, scientific submissions, nanotools, and devices that will be implemented to cure these types of complex medical conditions. Current notes on the pathophysiologic mechanisms of reperfusion after cerebral ischemia were observed and reviewed here. Cerebral ischemia-reperfusion injury is a medical condition that is induced by the deterioration of ischemic injury after reperfusion. Free radicals contribute to the initiation and propagation of cerebral ischemia-reperfusion injury and these radicals are one class of cytotoxic molecules responsible for these complications [2].

Figure 1

Free radicals are of two types i.e. the reactive oxygen species (ROS) and the reactive nitrogen species (RNS). ROS accumulation induces irregularities to cellular signal transduction and activate inflammation factors at the time of ischemia-reperfusion injury. Meanwhile, lipid peroxidation occur. These factors induce neural cell death, and as a result, the blood-brain barrier (BBB), lost natural functioning [3]. Overall, the enlargement of infarction transpired. The pathophysiology in the molecular context has several series events, including suboptimal Na+/K+ ATPases pump activity, and actions of microglia cytokines. These events trigger intracellular adhesion molecules. Overall, these routes support the WBC extravasation that has already been linked with the reactivity of matrix metalloproteinase. This networking of interconnected events can expose the phenomena of the pathology of oedema and apoptosis/inflammation [4]. In the end, glutamate activity trigger oxidative stress, enhanced Ca2+ concentration, and lipid peroxidation. These undesired events induce apoptosis. A proper identification of molecular targets that to be implemented in the treatment for stroke should have the potential and abilities to enhance biological and cellular events, including anti-apoptotic/ anti-inflammation, angiogenesis, optimal metabolism neurogenesis, anticoagulation/fibrinolysis effects, and anti-oxidation [5]. The elucidation and investigation of the pathophysiology of stroke and identification of the routes that can be implemented effectively during the treatment of stroke is the necessity of the hour. In these circumstances, authors tried their best to prepare a much-needed blueprint that can be a reality soon. A proper understanding of the role neutrophils, inflammatory signaling, and cytokines in brain injuries will be a bullet point during the clinical and physiological investigation of neuroinflammation and chronic neuroinflammatory diseases [6]. There the elucidation of the phenomenon of the immune system, including monocytes, macrophages, mast cells, neutrophils, basophils, dendritic cells, T-cells, and B-cells initiate redness, heat, swelling, pain, and loss of activity and function of the affected area at the time of infection [7].

Neutrophils and their constituent proteins reduce acute inflammatory conditions or insults, as well as participate in the recovery of chronic inflammatory diseases [8]. However, the role of neutrophils in neuroinflammation and chronic neuroinflammatory diseases is yet to be discovered. It is yet to be confirmed, but it was a firm belief that neutrophil extracellular traps modified the inflammatory and proceed with immune responses during injury at the location of infection and acute inflammation. Therefore, the role of NETs in sepsis, traumatic injury, ischemia-reperfusion-tempted injury, and its performance as potential markers is illustrated in the discussion [9]. Moreover, elucidation of therapeutic targets that can be useful for treating NET-related injury will be conferred. What are the roles of cytokines, what are the causes of initiation of acute inflammatory diseases, and how are cytokines involved in chronic inflammatory disease? These key aspects and queries are considered for further discussion and interconnected features are celebrated accordingly [10]. The cytokines, particularly TNFα and IL-1β, participate in the expansion and control of a CNS inflammatory response. Inflammatory mediators and inhibitors of peripheral inflammation are useful as a remedy in treating CNS injuries (stroke, head trauma, multiple sclerosis, Alzheimer’s disease). The cytokine tumor necrosis factor (TNF-alpha) is another component of the inflammatory routes that are being produced in the brain during infection, ischemia, and trauma [11]. Although this, TNF-alpha is also involved in brain immune and inflammatory activities. The TNF-alpha, a peptide, communicates with interleukin (IL)−6 and stimulates neutrophil chemoattractant, IL-1. Overall, these proteins direct infiltration of inflammatory cells at the site of injuries. In an earlier stage, TNF-alpha was found in neuronal cells near ischemic tissue (penumbra), later on, this peptide relocates in macrophages in the damaged tissue [12]. TNF-alpha has some features of pro-adhesive molecules and display them on the endothelium. These features and concerned activities initiate leukocyte accumulation, migration toward the brain, and adherence. The more important aspects of TNF-alpha are that they trigger glial cells, and so govern tissue remodeling, scar formation, and gliosis. Similarly, the cytokines are also proteins developed by cells, and performed as a networking molecule among cells for smooth functioning and act through cell receptors. The physiology of the cytokines has a deep association with neuroimmunology [13]. The common microbial product is known as muramyl peptide and endotoxin initiates the secretion of IL-1 and that IL-1. These molecules interact with neurohormones and neurotransmitters in the brain (Figure 2). These biochemical associations induce somatogenic activity in the concerned region [14].

Figure 2

It was also observed that TNF-α and interferon also stimulate somatogenic activities, but IL-2, IL-6, and TNFβ do not display these activities. Sleep regulation is considered an important phenomenon that takes part in the reactivation that is originated by neuropeptides, neurotransmitters, and biogenic amines. IL-1β shows better effectiveness comparatively TNF-α and IL-8 in initiating changes. Nausea and anorexia were detected in the form of adverse effects during the treatment when cytokines are applied as therapeutic. Author investigates the route of repairing of the brain ischemia, and reperfusion injury through a clinical and physiological exploration of neuroinflammation and chronic neuroinflammatory diseases [15]. These strategies can be applicable in near future for identifying therapeutic targets.

Author (Rajiv Kumar) gratefully acknowledges his younger brother Bitto for motivation. The author acknowledges bio render for providing the facility to illustrate the diagrams (Figures 1 & 2) and again acknowledges the same.

Wherever necessary, relevant citations are included in the reference section.

The author has declared that no competing interest exists.

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