Title : Investigating the effects of blast traumatic brain injury on the hypothalamus in a porcine model
Abstract:
The increasing prevalence of blast traumatic brain injury (bTBI) in military personnel has stimulated further research into this field. The neuroendocrine system can be severely affected in blast survivors and anterior pituitary dysfunction has been characterised in soldiers returning from service. Imaging studies have failed to report structural changes associated with hypopituitarism, which has prompted further investigation into hypothalamic disturbance in blast models. This study utilised a porcine model of bTBI to examine structural changes in the hypothalamus between bTBI animals (n=2) and non-bTBI (n=4) controls. Changes in microglial activation around the hypothalamus and differences in growth hormone releasing hormone (GHRH) expression were also examined.
Animals were categorised into blast (n=2), sham (n=2) and control (n=2) cases. Blast animals were subjected to an overpressure wave and systemic haemorrhage. Sham animals were only subject to systemic haemorrhage and control animals had no intervention. Animals were sacrificed 4 hours after intervention. Haematoxylin and eosin staining was used to examine structural differences. Anti-Iba1 and anti-GHRH immunohistochemistry was used to observe differences in microglial activation and GHRH expression, respectively.
Ventricular deformities such as parenchymal compression were noted in blast cases alone. There was evidence of sub-ependymal oedema in both blast and sham cases compared to control cases. Microglial activation was increased in both blast and sham cases compared to control cases. Furthermore, GHRH immunoreactivity was greatest in the porcine arcuate and paraventricular nucleus, however differential expression of GHRH could not be determined.
Evidence of structural damage to the hypothalamus was noted in bTBI animals and could provide a basis on which to explore hypothalamic damage in blast survivors. However, the pattern of neuroinflammation observed was likely attributable to systemic haemorrhage rather than blast exposure. Finally, anatomical landmarks such as the anterior fornix were associated with the localisation of GHRH secreting neurons in the pig.
What will audience learn from your presentation?
- Consider anterior pituitary dysfunction in blast injury survivors
- Hypothalamic damage may be due to both blast exposure and ischaemia in blast injury survivors
- Structural damage to midline structures is more prominent in traumatic blast injury, especially at phase interface such as the ventricular surface
- Neuroinflammation in blast injury is likely multifactorial but tackling this early could be an avenue in preventing long term hypothalamic dysfunction
