Neuronal Adhesion and Synapse Organization in Recovery After Brain Injury

Kellie Park; Thomas Biederer

Disclosures

Future Neurology. 2013;8(5):555-567. 

In This Article

Abstract and Introduction

Abstract

Few specific therapeutic targets exist to manage brain injury, despite the prevalence of stroke or traumatic brain injury. With traumatic brain injury, characteristic neuronal changes include axonal swelling and degeneration, and the loss of synapses, the sites of communication between neurons. This is followed by axonal sprouting and alterations in synaptic markers in recovery. The resulting changes in neuronal connectivity are likely to contribute to the effects of traumatic brain injury on cognitive functions and the underlying mechanisms may represent points of therapeutic intervention. In agreement, animal studies implicate adhesion and signaling molecules that organize synapses as molecular players in neuronal recovery. In this article, the authors focus on the role of cell surface interactions in the recovery after brain injury in humans and animals. The authors review cellular and synaptic alterations that occur with injury and how changes in cell adhesion, protein expression and modification may be involved in recovery. The changes in neuronal surface interactions as potential targets and their possible value for the development of therapeutics are also discussed.

Introduction

Traumatic brain injury (TBI) is a devastating problem worldwide. Approximately 2 million head injuries occur each year in the USA, which lead to over 50,000 deaths and approximately 80,000 individuals who survive with severe and permanent neurological dysfunction.[1] Unlike other types of brain injury such as stroke, TBI affects individuals of a broad range of ages. The mainstay of management of acute TBI is regulation of blood pressure and intracranial pressure to avoid secondary injury; however, few specific therapeutic targets exist for improvement of outcomes, such as cognitive deficits or post-traumatic epileptic seizures.[2] Approximately 43% of patients with severe injury develop cognitive dysfunction, as measured at 6-months follow-up, lasting for years after injury.[3,4] It is estimated that upwards of 40–50% of patients with severe injury develop post-traumatic seizures in as little as 1 week after injury with epilepsy lasting for years postinjury. Recent clinical trials show promise for potential therapeutics, including amantadine and progesterone.[5,6] However, studies on new and more specific clinical targets resulting in other therapeutics to treat TBI are warranted.[7] The authors propose, based on evidence provided in the studies below, that possible targets for new specific therapeutics include neuronal surface molecules and their signaling pathways. In this review, the authors discuss neuronal adhesion proteins in brain injury, and whether they may be potential targets for treatment after brain trauma.

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