Traumatic Brain Injury Induces Microglial and Caspase3 Activation in the Retina

Abstract

Traumatic brain injury (TBI) is among the main causes of sudden death after head trauma. These injuries can result in severe degeneration and neuronal cell death in the CNS, including the retina, which is a crucial part of the brain responsible for perceiving and transmitting visual information. The long-term effects of mild–repetitive TBI (rmTBI) are far less studied thus far, even though damage induced by repetitive injuries occurring in the brain is more common, especially amongst athletes. rmTBI can also have a detrimental effect on the retina and the pathophysiology of these injuries is likely to differ from severe TBI (sTBI) retinal injury. Here, we show how rmTBI and sTBI can differentially affect the retina. Our results indicate an increase in the number of activated microglial cells and Caspase3-positive cells in the retina in both traumatic models, suggesting a rise in the level of inflammation and cell death after TBI. The pattern of microglial activation appears distributed and widespread but differs amongst the various retinal layers. sTBI induced microglial activation in both the superficial and deep retinal layers. In contrast to sTBI, no significant change occurred following the repetitive mild injury in the superficial layer, only the deep layer (spanning from the inner nuclear layer to the outer plexiform layer) shows microglial activation. This difference suggests that alternate response mechanisms play a role in the case of the different TBI incidents. The Caspase3 activation pattern showed a uniform increase in both the superficial and deep layers of the retina. This suggests a different action in the course of the disease in sTBI and rmTBI models and points to the need for new diagnostic procedures. Our present results suggest that the retina might serve as such a model of head injuries since the retinal tissue reacts to both forms of TBI and is the most accessible part of the human brain.

Pathophysiology-Based Management of Secondary Injuries and Insults in TBI

“…The activation of caspase-3 occurred via extrinsic and intrinsic apoptotic pathways after TBI has been documented, and this response is also mirrored in the retina [ 118 ]. However, experimental studies suggest that when activation is sustained, calpain is more important than caspase-3 in mediating cell death after TBI [ 118 , 119 ].…”

“…The activation of caspase-3 occurred via extrinsic and intrinsic apoptotic pathways after TBI has been documented, and this response is also mirrored in the retina [ 118 ]. However, experimental studies suggest that when activation is sustained, calpain is more important than caspase-3 in mediating cell death after TBI [ 118 , 119 ]. The anti-apoptotic modulator B-cell lymphoma (Bcl-2) inhibits mPTP, preserving mitochondrial homeostasis and preventing mitochondrial Ca 2+ leak and programmed cell death [ 120 ].…”

Molecular Mechanisms of Retinal Degeneration and How to Avoid It

“…The retina is also prone to death and/or survival factors released by other brain areas affected by the primary insult. In a compelling research line, Kovacs-Öller and colleagues [8] investigated the differential effects of severe and random mild traumatic brain injuries (sTBI, rmTBI) in the retina. They showed that even mild injuries can lead to microglial activation in the ganglion cell layer on a level reminiscent of those following sTBI.…”