Alpha II Spectrin breakdown products in immature Sprague Dawley rat hippocampus and cortex after traumatic brain injury

Abstract

After traumatic brain injury (TBI), proteolysis of Alpha II Spectrin by Calpain 1 produces 145 SBDPs (Spectrin Breakdown Products) while proteolysis by Caspase 3 produces 120 SBDPs. 145 and 120 SBDP immunoblotting reflects the relative importance of caspase-dependent apoptosis or calpain-dependent excitotoxic/necrotoxic cell death in brain regions over time. In the adult rat, controlled cortical impact (CCI) increased 120 SBDPs in the first hours, lasting a few days, and increased 145 SBDPs within the first few days lasting up to 14 days after injury. Little is known about SBDPs in the immature brain after TBI. Since development affects susceptibility to apoptosis after TBI, we hypothesized that CCI would increase 145 and 120 SBDPs in the immature rat brain relative to SHAM during the first 3 and 5 days, respectively. SBDPs were measured in hippocampi and cortices at post injury days (PID) 1, 2, 3, 5, 7 and 14 after CCI or SHAM surgery in the 17 day old Sprague Dawley rat. 145 SBDPs increased in both brain tissues ipsilateral to injury during the first 3 days, while changes in contralateral tissues were limited to PID2 cortex. 145 SBDPs elevations were more marked and enduring in hippocampus than in cortex. Against expectations, 120 SBDPs only increased in PID1 hippocampus and PID2 cortex. 145 SBDPs elevations occurred early after CCI, similar to previous studies in the adult rat, but resolved more quickly. The minimal changes in 120 SBDPs suggest that calpain-dependent, but not caspase-dependent, cell death predominates in the 17 day old rat after CCI.

Imaging and serum biomarkers reflecting the functional efficacy of extended erythropoietin treatment in rats following infantile traumatic brain injury

“…The observed elevation in αII-SDPs is consistent with findings from other TBI studies. 8,70,86,107 While degradation of the cytoskeletal protein αII-S is a generic marker of neuronal injury, cerebral KCC2 levels more specifically reflect neuronal functional activity. In fact, KCC2 influences multiple components of neuronal activity including neuronal survival, inhibitory tone, synaptogenesis, and seizure threshold.…”

“…These initial studies demonstrate that excess CNS calpain activity occurs following P12 CCI, as in other preclinical models of TBI. 86 …”

“…1,87 Controlled cortical impact produces contusion and injury in the cortex, white matter, and hippocampus immediately beneath the impact and diffuse injury in the hemisphere contralateral to the impact. 10,27,86 Unlike fluid percussion models that have been increasingly used to study sports concussion and blast-induced TBI, CCI mimics biomechanical events contributing to injury such as the force and tissue deformation common to mechanisms in infants with head injury.…”

Blast waves from detonated military explosive reduce GluR1 and synaptophysin levels in hippocampal slice cultures

“…The hippocampus is the main focus of this study not only due to it being distinctly vulnerable to traumatic and excitotoxic injuries, but also because it is a region that is important for higher order brain functions, that expresses synaptic plasticity to compute diverse information, and that is involved in routing encoded spatial, emotional, and reward information to other brain areas (see Bahr et al, 1998; Szinyei et al, 1999; Pelletier and Lacaille, 2008; Schober et al, 2014; Carlson et al, 2015; Ciocchi et al, 2015). The organotypic cultures allow studies to address specific issues in the absence of systemic variables, thus avoiding interpretation issues in the present study regarding whether subtle vs. severe neuronal changes are produced by single or multiple RDX blasts.…”

The role of βII spectrin in cardiac health and disease

“…Spectrin breakdown products (SBDPs) are produced by calpain- and caspase-3-mediated mechanisms and can be detected in the cerebrospinal fluid (CSF) [112–114] and serum [115]. In brain, αII spectrin is degraded by calpain into 2 main fragments (150 kDa and 145 kDa) while caspase-3-induced proteolysis results in the formation of a 150 kDa fragment which is further degraded yielding a 120 kDa spectrin breakdown product [116–120].…”