Neuronal death after brain injury

Abstract

Neuronal damage in the central nervous system leads to primary cell death, induced directly by the trauma, and delayed secondary death of neurons, the latter depending on environmental changes, lack of metabolic and trophic supply, and altered gene transcription. While primary death of neurons occurring within a short time after trauma is not a realistic target for therapy, secondary cell death might be prevented by new neuroprotective strategies. Although there are increasing data concerning cell rescue after ischemic and traumatic brain injury through the last decade, the mechanisms that underlie secondary death of neurons following lesion are still incompletely understood and are now the subject of a more detailed investigation. In this review, we want to give an overview on what is known about the molecular mechanisms of delayed ischemic and traumatic neuronal death in vivo and about promising neuroprotective treatment strategies that might be of future clinical relevance or have already entered clinical trials.

Optic nerve crush induces spatial and temporal gene expression patterns in retina and optic nerve of BALB/cJ mice

“…Changes in gene expression in rodent ONC models have been previously studied [22,26-30] and include gap associated protein 43 ( Gap43 ) [31-33], glial fibrillary acidic protein ( Gfap ) [34-36] and neurofilament deregulation after crush injury [37]. Furthermore, progressive retinal ganglion cell (RGC) degeneration has been associated with loss of trophic support [38,39], stimulation of inflammatory processes/immune regulation [40,41], and apoptotic effectors [39,42-45]. In addition, multiple injury models have been utilized to assess the fate of RGCs after ocular injuries that include ischemia/reperfusion, ON irradiation, ON transections, and traumatic ON injury in rodent and primate models [22,30,46-50].…”

“…Although previous studies with CNS trauma models have addressed gene expression changes related to neuronal apoptosis [18,26,39,51], current gaps still exist for identifying long-term neuroprotective and regeneration inducing targets. Additionally, most expression studies for the ONC model have only been performed in the retina or the optic nerve head [3,22,29].…”

The competitive NMDA receptor antagonist CPP disrupts cocaine-induced conditioned place preference, but spares behavioral sensitization

“…MK801 acts within the NMDA calcium channel in a manner similar to phencyclidine (PCP) and ketamine, and can produce psychosis [37], catalepsy, analgesia, and locomotor hyperactivity. Indeed, most noncompetitive NMDAR antagonists, because of their similarity to PCP, have been proposed as animal models of schizophrenia [38].…”

Bilateral Decompressive Craniectomy for Refractory Intracranial Hypertension in a Child with Severe ITP-Related Intracerebral Haemorrhage

“…This secondary damage is the result of a sequence of events that can include: disruption of the normal regulation of cerebral inflow and outflow, often resulting in cerebral hyperaemia; increased transmural pressure in capillary beds causing tissue hypoxia, elevated levels of CO 2 and a reduction in extravascular fluid resorption; tissue acidosis; metabolic dysfunction; microthrombus formation; secondary inflammation, and damage to the blood-brain barrier, all of which increase cerebral oedema and cause further increases in ICP [32,33,34,35,36,37,38,39,40,41,42,43]. The brain of a child, and particularly of a young child, may be particularly susceptible to these pathophysiological changes.…”