Changes in Calcium-Binding Protein Expression in Human Cortical Contusion Tissue

Abstract

Traumatic brain injury (TBI) produces several cellular changes, such as gliosis, axonal and dendritic plasticity, and inhibition-excitation imbalance, as well as cell death, which can initiate epileptogenesis. It has been demonstrated that dysfunction of the inhibitory components of the cerebral cortex after injury may cause status epilepticus in experimental models; we proposed to analyze the response of cortical interneurons and astrocytes after TBI in humans. Twelve contusion samples were evaluated, identifying the expression of glial fibrillary acidic protein (GFAP) and calcium-binding proteins (CaBPs). The study was made in sectors with and without preserved cytoarchitecture evaluated with NeuN immunoreactivity (IR). In sectors with total loss of NeuN-IR the results showed a remarkable loss of CaBP-IR both in neuropil and somata. In sectors with conserved cytoarchitecture less drastic changes in CaBP-IR were detected. These changes include a decrease in the amount of parvalbumin (PV-IR) neurons in layer II, an increase of calbindin (CB-IR) neurons in layers III and V, and an increase in calretinin (CR-IR) neurons in layer II. We also observed glial fibrillary acidic protein immunoreactivity (GFAP-IR) in the white matter, in the gray-white matter transition, and around the sectors with NeuN-IR total loss. These findings may reflect dynamic activity as a consequence of the lesion that is associated with changes in the excitatory circuits of neighboring hyperactivated glutamatergic neurons, possibly due to the primary impact, or secondary events such as hypoxia-ischemia. Temporal evolution of these changes may be the substrate linking severe cortical contusion and the resulting epileptogenic activity observed in some patients.

Age-related loss of calcium buffering and selective neuronal vulnerability in Alzheimer’s disease

“…Some modes of neuronal damage may be associated with upregulation of CB [9, 27]. To determine whether the presence of CB in nearly all AD BFCN is due to upregulation of this protein rather than preservation of CB containing neurons, we collected AD BFCN from fresh frozen tissue sections using laser capture microdissection and determined the levels of CB RNA by quantitative real-time PCR.…”

Imaging biomarkers of posttraumatic epileptogenesis

“…Early studies have proposed that PTE was caused by the formation of gliosis, 19 but recent research has advanced additional molecular and neuronal changes that coincide with epileptogenesis, including inflammation, 8 blood-brain barrier (BBB) disruption, 20 loss of neurons and glia, 8,21,22 and axonal and dendritic plasticity. 8,21,22 It has not been confirmed if these specific changes are epileptogenic, or unrelated consequences of brain trauma. To date, imaging has focused on the definition of primary lesion formation and evolution of gliosis, but there is potential for imaging to inform pathomechanisms of PTE (see Table 1 for review).…”

Epilepsy Related to Traumatic Brain Injury

“…Tomkins et al [56] pointed out the possible role of BBB damage in PTE by showing that cortical BBB permeability was higher in TBI patients with epilepsy than those without, whereas the size of cortical lesion did not differ. Interestingly, a recent analysis of the resected pericontusional cortex demonstrated remarkable degeneration of subpopulations of inhibitory neurons, but no information was available about whether any of these patients developed epilepsy in follow-up [57,58].…”