Understanding Acquired Brain Injury: A Review

Abstract

Any type of brain injury that transpires post-birth is referred to as Acquired Brain Injury (ABI). In general, ABI does not result from congenital disorders, degenerative diseases, or by brain trauma at birth. Although the human brain is protected from the external world by layers of tissues and bone, floating in nutrient-rich cerebrospinal fluid (CSF); it remains susceptible to harm and impairment. Brain damage resulting from ABI leads to changes in the normal neuronal tissue activity and/or structure in one or multiple areas of the brain, which can often affect normal brain functions. Impairment sustained from an ABI can last anywhere from days to a lifetime depending on the severity of the injury; however, many patients face trouble integrating themselves back into the community due to possible psychological and physiological outcomes. In this review, we discuss ABI pathologies, their types, and cellular mechanisms and summarize the therapeutic approaches for a better understanding of the subject and to create awareness among the public.

Keywords: Acquired Brain Injury (ABI); brain functions; brain impairment; cellular mechanisms; pathologies; post-birth; therapeutic approach.

Figure 1

ABI: Etiopathology, classifications, the brain region affected, and related complications. The pictorial presentation of ABI describes its type (purple) and etiology of the disease (in orange texts). ABI is mainly divided into TBI and Non-TBI injuries. Non-TBI can arise from tumors, vessel occlusion, infection, or alcohol consumption. ABI can affect different regions of the brain depending on impact, insult, infection, or blockage (shown in pink) and may show related signs and symptoms (depicted in green). HR: Heart rate.

Figure 2

Poor outcomes post-ABI. A variety of parameters related to the ABI mechanism play a role in predicting the outcome. ABI can develop as a result of a stroke or disease or an iatrogenic cause, and there is some indication that those who suffer from a head injury are a self-selecting group, with poor attention, impulsivity, and overactivity being associated with poor road-crossing skills. These may interact with other premorbid characteristics that are predictors of poor post-injury prognosis.

Figure 3

Schematic representation of pathophysiology of ABI. BBB dysfunction caused by injury allows the transmigration of activated leukocytes into the injured brain parenchyma, which is facilitated by the upregulation of cell adhesion molecules. Activated leukocytes, microglia, and astrocytes produce ROS and inflammatory molecules such as cytokines and chemokines that contribute to demyelination and disruption of the axonal cytoskeleton, leading to axonal swelling and accumulation of transport proteins at the terminals. On the other hand, excessive accumulation of glutamate and aspartate neurotransmitters in the synaptic space due to spillage from severed neurons activates NMDA and AMDA receptors located on post-synaptic membranes, which allow the production of ROS. As a result of mitochondrial dysfunction, molecules such as apoptosis-inducing factor (AIF) and cytochrome c are released into the cytosol. These cellular and molecular events including the interaction of Fas with its ligand Fas ligand (FasL) ultimately lead to caspase-dependent and -independent neuronal cell death. BBB: blood-brain barrier; NMDA: N-methyl-D-aspartate receptor; AMPA: α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor; ROS: Reactive oxygen species; Cyt c: Cytochrome c; ICP: Intracranial pressure; AIF: Apoptosis-inducing factor.

Figure 4

Expected molecular mechanism of brain injury on tau in the nervous system. Neurons, glia, oligodendrocytes, and blood vessels are damaged by the impact load that arises after a head injury. Injury to some or more of these cells causes intracellular unfolding, which causes the entire device to malfunction. Tau, which is highly correlated with microtubules, is abundant in axons. Impact forces devastate cell membrane integrity, as well as the microtubule framework in the axon. Tau disengages from the microtubule as it becomes unstable. Tau would then be misfolded, phosphorylated, develop a porous oligomeric conformation, accumulate, or disperse in a dysfunctional pathway. Tau may also invade other neighboring cells (glia, serum, or CSF) as it spreads.