From Cell Death to Neuronal Regeneration: Building a New Brain after Traumatic Brain Injury

Abstract

During the past decade, there has been accumulating evidence of the involvement of passive and active cell death mechanisms in both the clinical setting and in experimental models of traumatic brain injury (TBI). Traditionally, research for a treatment of TBI consists of strategies to prevent cell death using acute pharmacological therapy. However, to date, encouraging experimental work has not been translated into successful clinical trials. The development of cell replacement therapies may offer an alternative or a complementary strategy for the treatment of TBI. Recent experimental studies have identified a variety of candidate cell lines for transplantation into the injured CNS. Additionally, the characterization of the neurogenic potential of specific regions of the adult mammalian brain and the elucidation of the molecular controls underlying regeneration may allow for the development of neuronal replacement therapies that do not require transplantation of exogenous cells. These novel strategies may represent a new opportunity of great interest for delayed intervention in patients with TBI.

Lovastatin improves histological and functional outcomes and reduces inflammation after experimental traumatic brain injury

“…A secondary finding is that lovastatin improved both functional and histological outcomes; this is of considerable importance because pre-clinical studies combing both histological and neurobehavioral evaluations may improve the predictive value of animal models for clinical efficacy with novel neuroprotective agents (Hunter et al, 1998). In experimental models of TBI, delayed neuronal cell death occurs in the boundary zone of the injured cortical area, apart from the area of primary neuronal necrosis (Royo et al, 2003). It is delayed cell loss that subsequently contributes to neurological functional deficits (Fox et al, 1998).…”

Strategies for CNS repair following TBI

“…As a result of these processes, necrotic cell death predominates in the acute setting and is followed by a prolonged period during which apoptosis occurs (Royo et al, 2003). Apoptosis following TBI has been described as biphasic in nature.…”

A decade from discovery to therapy: Lingo-1, the dark horse in neurological and psychiatric disorders

“…Traumatic brain injury characteristically involves the necrotic and apoptotic death of cells in the brain in vulnerable areas such as the cerebral cortex and hippocampus (Conti et al, 1998;Raghupathi, 2004;Royo et al, 2003), two areas known to highly express Lingo-1 in both the adult stage of life and throughout development (Carim-Todd et al, 2003;Mi et al, 2004). RhoA signaling is largely responsible for the neuronal response to neuronal inhibitory proteins and the regeneration (or lack thereof) of damaged axons (Dubreuil et al, 2006).…”