Roles of Pro- and Anti-inflammatory Cytokines in Traumatic Brain Injury and Acute Ischemic Stroke

Abstract

This chapter will introduce the reader to the pathophysiology of two devastating neurologic events, traumatic brain injury (TBI) and acute ischemic stroke (AIS). Here we focus on the role of key pro-inlammatory and anti-inlammatory cytokines. Several experimental interventions have been found to modulate cytokine production and brain injury after AIS or TBI. Here minocycline, biological response modiiers, hormonal therapies, omega-3 faty acids, N-acetylcysteine, and cannabinoids will be discussed. In addition, the role of cytokine-induced inlammasomes in both TBI and AIS will be addressed and followed by discussion of pro-inlammatory cytokines (e.g., TNF-α, IL-1β, IL-18, and IFN-γ). Finally, the main anti-inlammatory cytokines, IL-33, IL-10, IL-6, and IL-4, will be discussed in the context of both TBI and AIS. It should be noted that the role of these cytokines is diverse and the dichotomization of classically pro-versus anti-inlammatory cytokines is being re-examined, as many of these cytokines have been found to play dual roles in TBI and AIS brain injury.Keywords: traumatic brain injury, ischemic stroke, cytokines, interleukins, inlammasome Pathophysiology of traumatic brain injuryTraumatic brain injury (TBI) is a major cause of death and disability worldwide [1,2]. It is one of the most commonly diagnosed neurological disorders in the United States, impacting people of a variety of ages and segments of society [3]. In Europe, the economic cost of © 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.TBI is over 33 billion euros per year [4]. Continued surveillance and research is being done to reduce primary and secondary TBI [as well as acute ischemic stroke(AIS)]-induced brain injury [1].The pathophysiology of TBI begins with the initial brain trauma (i.e., the primary injury). This primary injury results from mechanical damage that disrupts the blood-brain barrier (BBB), alters the vasculature and damages brain tissue. The resulting injured glia and neurons release their intracellular contents (i.e., damage-associated molecular paterns; (DAMPs)) into the extracellular space and activate neighboring glia and neurons. Activated glia and neurons then produce molecular signals that can both exacerbate and mend the acute injury and contribute to long-term recovery [5][6][7][8][9]. These downstream molecular and cellular processes (i.e., the secondary injury in TBI) are the focus of many pre-clinical and clinical therapeutic studies. Secondary injury in TBI involves a host of molecular and cellular responses to the The pathophysiology of AIS and TBI share common mechanisms. The initial insult in AIS, an occlusion of blood low resulting in a core infarct zone surrounded by a poorly perfused penumbra, versus the initial primary physical impact in TBI both result in pe...

Perispinal etanercept advances as a neurotherapeutic

“…When in excess, TNF interferes with neurotransmission, perturbs brain function, and mediates neuropathic pain [2][3][4][5][6][7][8][9]. Excess TNF is centrally involved in the initiation and maintenance of neuroinflammation, an area of accelerating interest in the field of neurology [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Bioengineered TNF inhibitors are natural candidates for study in clinical trials of neuroinflammatory disorders .…”

“…Neurological improvements in these patients have included favorable changes in gait, spasticity, mental function, aphasia, sensation, and chronic poststroke pain and a host of less common, but no less important improvements, including improvements in special senses, bladder function, etc [20,22,23]. Since 2010, the scientific rationale has been strengthened by at least six favorable studies of etanercept in stroke models and three favorable randomized clinical trials of etanercept for spinal neuropathic pain (cited in [21]); see also [2,[6][7][8][9][10][12][13][14][15]18,20,24,25].…”

“…Other recent developments have also been significant. There is increasing recognition in the scientific community of the role of excess TNF in the pathophysiology of neuroinflammation, with hundreds of citations to scientific publications involving PSE treatment for spinal pain, AD, stroke, and TBI [1][2][3][4][5][6][7][8][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. A Google Scholar search of 'PSE' currently yields 680 results, one measure of the scholarly interest that these scientific publications have generated.…”

Neuroinflammation: friend and foe for ischemic stroke

“…Ischemic stroke is characterized by arterial occlusion due to embolus or thrombus [5]. The functional and metabolic irregularities that occur during ischemic stroke largely depend on the artery that is occluded, which in turn determines the size of the ischemic area in the brain [6].…”

Experimental Pretreatment with Chlorogenic Acid Prevents Transient Ischemia-Induced Cognitive Decline and Neuronal Damage in the Hippocampus through Anti-Oxidative and Anti-Inflammatory Effects

“…Since the brain is well known to be an aseptic organ, and pathogens are not involved in the neuroinflammatory response following ischemia-reperfusion injury, some studies call this response a “sterile inflammatory response” [ 46 , 48 ]. In addition, neuroinflammation is concerned with both beneficial and detrimental roles in ischemic brains, and these are modulated by anti- and pro-inflammatory cytokines [ 49 , 50 , 51 ]. It is well known that pro-inflammatory cytokines exacerbate and advance deleterious inflammatory processes, but anti-inflammatory cytokines suppress the expressions of pro-inflammatory cytokines and bring advantageous inflammatory processes in ischemic brains [ 10 , 52 ].…”