Neurotrauma: The Crosstalk between Neurotrophins and Inflammation in the Acutely Injured Brain

Abstract

Traumatic brain injury (TBI) is a major cause of morbidity and mortality among young individuals worldwide. Understanding the pathophysiology of neurotrauma is crucial for the development of more effective therapeutic strategies. After the trauma occurs, immediate neurologic damage is produced by the traumatic forces; this primary injury triggers a secondary wave of biochemical cascades together with metabolic and cellular changes, called secondary neural injury. In the scenario of the acutely injured brain, the ongoing secondary injury results in ischemia and edema culminating in an uncontrollable increase in intracranial pressure. These areas of secondary injury progression, or areas of “traumatic penumbra”, represent crucial targets for therapeutic interventions. Neurotrophins are a class of signaling molecules that promote survival and/or maintenance of neurons. They also stimulate axonal growth, synaptic plasticity, and neurotransmitter synthesis and release. Therefore, this review focuses on the role of neurotrophins in the acute post-injury response. Here, we discuss possible endogenous neuroprotective mechanisms of neurotrophins in the prevailing environment surrounding the injured areas, and highlight the crosstalk between neurotrophins and inflammation with focus on neurovascular unit cells, particularly pericytes. The perspective is that neurotrophins may represent promising targets for research on neuroprotective and neurorestorative processes in the short-term following TBI.

Interhemispherically dynamic representation of an eye movement-related activity in mouse frontal cortex

“…This damage initiates highly complex pathophysiologic reactions like inflammation and reactive gliosis, which leads to the upregulation of neurotrophic factors and pro-inflammatory cytokines. All of these reactions could, in principle, be involved in plasticity (Alia et al, 2017; da Silva Meirelles et al, 2017; Fawcett, 2015; Li et al, 2010). Therefore, it was not clear whether functional recovery could be achieved without complex pathophysiological events triggered by cortical lesions.…”

Neurobehavioral, Cognitive, and Paroxysmal Disorders in the Long-Term Period of Pediatric Traumatic Brain Injury

“…The brain preserves a capacity to recover and adapt secondary compensatory mechanisms when neural tissue is compromised. This capability is due to neuroplasticity, a unique feature that makes the neural circuits malleable and is at the basis of memory formation and learning as well as in adapting to injuries and traumatic events throughout life [53][54][55][56].…”

“…The pharmacological potential of neuropeptides is linked with the treatment of cerebral diseases associated with secondary brain damage, including TBI. Specifically, in the area of "traumatic penumbra," neurotrophins may offer protection from a secondary injury by stimulating growth and differentiation and promoting recovery of injured brain neurons [53].…”

Neuroimmune System as a Driving Force for Plasticity Following CNS Injury

“…Coupled with endogenous alarmins, antigens, and inflammatory signals, this microglial response further stimulates the infiltration of neutrophils, monocytes/macrophages, lymphocytes, and dendritic cells to the injury site (Donnelly and Popovich, 2008 ). These temporal cascades are further correlated with increased expression of inflammatory mediators [e.g., tumor necrosis factor-alpha (TNFα), IL-1β, IL-6, reactive oxygen species (ROS), etc.,] and neurotrophic factors [e.g., brain-derived neurotrophic factor (BDNF), glial cell-line derived neurotrophic factor (GDNF), nerve growth factor (NGF), NT-3, etc., Donnelly and Popovich, 2008 ; Jin et al, 2010 ; da Silva Meirelles et al, 2017 ], which contribute to driving cellular, axonal, and anatomical plasticity described below in more detail.…”