Abstract
Purpose: :
Traumatic brain injury (TBI) is both the leading cause of death and disability among children and young adults (CDC report, 2004), as well as the signature injury in the War on Terrorism (USA Today, 2007). Post-trauma vision syndrome (PTVS), a frequent secondary effect encountered in the brain-injured population, results in a wide variety of visually debilitating deficits and oculomotor dysfunction. However, since visual symptoms/complaints caused by TBIs are not always associated with overt ocular health issues, rehabilitation is considerably lengthened and impaired. While the mechanism underlying PTVS is unclear, it may be causally associated with well known pathologies that occur after TBI, such as induction of the inflammatory response. Therefore, this study uses a well-characterized model of diffuse TBI to investigate 1) the inflammatory response along the visual pathway; and 2) correlate these findings with histopathologic alteration in the same pathway, all of which allows us to better understand the causative factors and ultimately improve diagnosis, treatment and rehabilitation.
Methods: :
TBI was induced in male Sprague-Dawley rats (350-400 g) using a weight drop (450 g, 2 m height) acceleration impact model modified after Marmarou et al (1994). Superior colliculus, optic tract, optic nerve, posterior eye and cornea were collected at 0, 4, 24 and 48 h post-injury (n = 3/time point) and processed for either histopathology or mRNA analysis using RT2 ProfilerTM PCR Array.
Results: :
Eighty-four inflammatory cytokine/chemokine and receptor genes were examined by real-time RT-PCR. Compared to tissues from 0 h controls (sham), many pro- and anti-inflammatory molecules were differentially expressed in all analyzed regional components of the visual pathway at 24 and 48 h post-injury. Histopathologic alterations at similar end points further supported the presence of a strong inflammatory response.
Conclusions: :
This study is first to show concurrent inflammation in functionally related structures along the visual pathway. The correlative mRNA and histopathologic findings support the notion that inflammation may underlie PTVS. Future studies will aim to target components of the inflammatory response in an effort to improve effects on the visual system.
Keywords: inflammation • pathology: experimental • neuro-ophthalmology: diagnosis