Clinical significance of alphaII-spectrin breakdown products in cerebrospinal fluid after severe traumatic brain injury.

Following traumatic brain injury (TBI), the cytoskeletal protein alpha-II-spectrin is proteolyzed by calpain and caspase-3 to signature breakdown products. To determine whether alpha -II-spectrin proteolysis is a potentially reliable biomarker for TBI in humans, the present study (1) examined levels of spectrin breakdown products (SBDPs) in cerebrospinal fluid (CSF) from adults with severe TBI and (2) examined the relationship between these levels, severity of injury, and clinical outcome. This prospective case control study enrolled 41 patients with severe TBI, defined by a Glasgow Coma Scale (GCS) score of < or =8, who underwent intraventricular intracranial pressure monitoring. Patients without TBI requiring CSF drainage for other medical reasons served as controls. Ventricular CSF was sampled from each patient at 6, 12, 24, 48, 72, 96, and 120 h following TBI and analyzed for SBDPs. Outcome was assessed using the Glasgow Outcome Score (GOS) 6 months after injury. Calpain and caspase-3 mediated SBDP levels in CSF were significantly increased in TBI patients at several time points after injury, compared to control subjects. The time course of calpain mediated SBDP150 and SBDP145 differed from that of caspase-3 mediated SBDP120 during the post-injury period examined. Mean SBDP densitometry values measured early after injury correlated with severity of injury, computed tomography (CT) scan findings, and outcome at 6 months post-injury. Taken together, these results support that alpha -II-spectrin breakdown products are potentially useful biomarker of severe TBI in humans. Our data further suggests that both necrotic/oncotic and apoptotic cell death mechanisms are activated in humans following severe TBI, but with a different time course after injury.

Increased expression of calponin-3 in epileptic patients and experimental rats.

Calponin-3 is an actin-interacting protein and is expressed in the brain. Our previous microarray scan has found an up-regulation of calponin-3 gene CNN3 in the temporal lobe of patients with drug-resistant epilepsy. Here we investigated in epileptic patients the changes of brain and cerebrospinal fluid (CSF) calponin-3 expressions, and assessed calponin-3 expression pattern in a rat model of pilocarpine-induced epilepsy. We showed that in the temporal neocortices of 30 patients with drug-resistant epilepsy, both mRNA and protein level of calponin-3 were significantly increased. In addition, the augmentation of CSF calponin-3 from 126 epileptic patients was closely correlated with disease duration. Moreover, in the cortices of temporal lobes of pilocarpine-treated rats, calponin-3 increased along with the time and maintained at significant high levels for up to 2 months, while the up-regulation of hippocampal calponin-3 only occurred at 24h and 1 week. The elevated calponin-3 suggests that deregulation of actin filament dynamics in axonal and dendritic outgrowth and synaptic rearrangement may contribute to pathophysiology of epilepsy.