Temporal characterisation of pro- and anti-apoptotic mechanisms following diffuse traumatic brain injury in rats

Ibolja Cernak, Sarah M. Chapman, Gary P. Hamlin, Robert Vink

Research output: Contribution to journalArticleResearchpeer-review

39 Citations (Scopus)

Abstract

Few studies have characterised apoptosis in a brain injury model that causes a significant degree of diffuse axonal injury. Such Such characterisation is essential from a clinical viewpoint since diffuse axonal injury is a major component of human head injury. The present study therefore, examines the expression of active and proactive caspase-3, and the bax, bcl-2 and bcl-x members of the bcl-2 family, to characterise the temporal profile of apoptosis in a model of traumatic brain injury in rats that produces significant diffuse axonal injury. Pentobarbital anaesthetised male Sprague-Dawley rats were injured using the 2m impact-acceleration model of diffuse traumatic brain injury. After injury, diffuse trauma resulted in an increased bax expression followed by induction of caspase-3. The increase in caspase-3 was simultaneous with an increase in anti-apoptotic bcl-2 expression. Bcl-x levels were increased after induction of caspase-3 and the increased levels of bcl-x were sustained to the end of the 5-day observation period. Increased active caspase-3 expression was associated with the appearance of TUNEL positive cells. These cells were detected in different brain regions at different times, with some regions showing no apoptotic cells until 3 days after injury. No TUNEL positive cells were detected at 7 and 14 days after injury. DNA electrophoresis confirmed that DNA fragmentation was maximal at 3 days after injury. Increased active caspase-3 levels were also significantly correlated with increased bcl-2 levels (r=0.80; P<0.001) suggesting that the apoptotic cascade after diffuse traumatic brain injury is a carefully controlled cellular homeostatic response. Pharmacological manipulation of this balance may offer a therapeutic approach for preventing cell death and improving outcome after diffuse traumatic brain injury.

Original languageEnglish
Pages (from-to)565-572
Number of pages8
JournalJournal of Clinical Neuroscience
Volume9
Issue number5
DOIs
Publication statusPublished - 1 Jan 2002
Externally publishedYes

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Caspase 3
Diffuse Axonal Injury
Wounds and Injuries
In Situ Nick-End Labeling
Apoptosis
DNA Fragmentation
Pentobarbital
Craniocerebral Trauma
Brain Injuries
Sprague Dawley Rats
Electrophoresis
Diffuse Brain Injury
Traumatic Brain Injury
Cell Death
Observation
Pharmacology
DNA
Brain

Cite this

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abstract = "Few studies have characterised apoptosis in a brain injury model that causes a significant degree of diffuse axonal injury. Such Such characterisation is essential from a clinical viewpoint since diffuse axonal injury is a major component of human head injury. The present study therefore, examines the expression of active and proactive caspase-3, and the bax, bcl-2 and bcl-x members of the bcl-2 family, to characterise the temporal profile of apoptosis in a model of traumatic brain injury in rats that produces significant diffuse axonal injury. Pentobarbital anaesthetised male Sprague-Dawley rats were injured using the 2m impact-acceleration model of diffuse traumatic brain injury. After injury, diffuse trauma resulted in an increased bax expression followed by induction of caspase-3. The increase in caspase-3 was simultaneous with an increase in anti-apoptotic bcl-2 expression. Bcl-x levels were increased after induction of caspase-3 and the increased levels of bcl-x were sustained to the end of the 5-day observation period. Increased active caspase-3 expression was associated with the appearance of TUNEL positive cells. These cells were detected in different brain regions at different times, with some regions showing no apoptotic cells until 3 days after injury. No TUNEL positive cells were detected at 7 and 14 days after injury. DNA electrophoresis confirmed that DNA fragmentation was maximal at 3 days after injury. Increased active caspase-3 levels were also significantly correlated with increased bcl-2 levels (r=0.80; P<0.001) suggesting that the apoptotic cascade after diffuse traumatic brain injury is a carefully controlled cellular homeostatic response. Pharmacological manipulation of this balance may offer a therapeutic approach for preventing cell death and improving outcome after diffuse traumatic brain injury.",
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Temporal characterisation of pro- and anti-apoptotic mechanisms following diffuse traumatic brain injury in rats. / Cernak, Ibolja; Chapman, Sarah M.; Hamlin, Gary P.; Vink, Robert.

In: Journal of Clinical Neuroscience, Vol. 9, No. 5, 01.01.2002, p. 565-572.

Research output: Contribution to journalArticleResearchpeer-review

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