This blog has concentrated on the impact of traumatic brain injury (TBI) on the neurologic and visual function of the person as a whole. But much is going on in the human brain and eyes on the much smaller cellular level. Cells are the essential building blocks of all physiologic function.
The difficultly in any cellular or molecular discussion of TBI is that the conversation quickly becomes technical and this blog is intended to reach a broader audience. But details cannot be ignored.
Neurons in the brain communicate with each other by using neurotransmitters (chemicals in the brain). The substance glutamate is found in high concentrations within brain cells- it is the brain’s most common neurotransmitter.
The release of glutamate in TBI can occur when neural membranes are stretched. Once the glutamate exists in the cell, it can do a lot of damage. Outside the cell, it can create a sequence of events leading to cell death. Many therapeutic drug studies have been initiated with drugs that block extracellular glutamate, but so far no big clinical successes.
Elevated levels of intracellular calcium can cause neuron cell damage and death. Calcium channels in the cell’s outer membrane closely regulate this important ion in cell function. Once these delicate channels are disrupted by trauma, bad things happen. Calcium can activate a group of larger molecules called calpains which are supposed to clean up the mess, but in high concentrations these calpains make things worse. This is a common theme in brain injury- the chemicals that are supposed to protect the brain in low quantities can have the opposite effect when released suddenly during trauma.
The hippocampus is a part of the brain very important to neurocognitive function. The hippocampus seems to be particularly sensitive to cell death in TBI.
Apoptosis is a an interesting cellular mechanism where damaged cells actually commit suicide and destroy themselves before they can become cancerous. Apoptosis appears to be turned on in TBI leading to a secondary wave of needless cell death.
Mitochondria, which are little organs within a cell, are critical to cell well-being. These same mitichondria are damaged in TBI. A drug called Cyclosporine is already used to prevent transplant rejection in patients needing donor organ transplants. This same drug seems to have a neuroprotective effect in brain injury patients and since it is not a new drug it is already being tested in clinical studies to see if it benefits humans suffering brain injury.
This subject is complicated. A common theme in medicine, which appears to be true in TBI, is the body’s efforts to repair initial damage are often counter-productive and lead to a second wave of cell death. This correlates with the observation that certain patients do well after initial TBI but deteriorate at a later point in time.
I always try to relate my discussion to the eye. The photoreceptors, bipolar cells, and ganglion cells of the retina are very similar to the neurons in the brain. These cells are also damaged in TBI, but unlike the cells in the brain, they are not hidden from immediate and direct observation.
Optical Coherence Tomography provides a highly-magnified direct picture of individual cells. Thus, the eyes may be a useful model for estimating brain cell damage. Also , TBI can cause changes in the vitreous (a gel in front of the retina) and small amounts of bleeding in the retina, but nobody ever looks. Once again the value of a detailed retinal exam by a trained ophthalmologist is critical. I’ve made this point before- we must realize the eyes are not protected by a hard closed skull- they sit on the surface of the head and experience the direct impact of trauma.
Steven H. Rauchman, M.D. is an eye physician and surgeon who has been in private practice for 30 years. He has served as a Traumatic Brain Injury (TBI) medical/legal expert for the last 6 years specializing in the area of personal injury and related traumatic brain injuries.