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Investigations on Alterations of Hippocampal Circuit Function Following Mild Traumatic Brain Injury
Published on: November 19, 2012
Alpha II Spectrin breakdown products in immature Sprague Dawley rat hippocampus and cortex after traumatic brain
Michelle E Schober1, Daniela F Requena2, Lizeth J Davis2
1Department of Pediatrics, Division of Critical Care, University of Utah School of Medicine, Salt Lake City, UT 84132, United States.
Insights
Traumatic brain injury (TBI) in young rats showed increased 145 Spectrin breakdown products (SBDPs) early after injury, indicating predominantly calpain-dependent cell death. Minimal 120 SBDPs suggest less caspase-dependent cell death in immature brains.
Area of Science:
- Neuroscience
- Cell Biology
- Traumatic Brain Injury Research
Background:
- Alpha II Spectrin proteolysis yields 145 Spectrin breakdown products (SBDPs) via Calpain 1 and 120 SBDPs via Caspase 3.
- SBDP levels indicate the relative importance of calpain-dependent (excitotoxic/necrotic) and caspase-dependent (apoptotic) cell death pathways post-TBI.
- Limited data exists on SBDPs in immature brains following TBI, despite developmental differences in apoptosis susceptibility.
Purpose of the Study:
- To investigate the temporal and regional changes in 145 and 120 SBDPs in the immature rat brain after controlled cortical impact (CCI).
- To compare SBDP profiles in immature versus adult brains to understand developmental influences on TBI-induced cell death pathways.
Main Methods:
- Controlled cortical impact (CCI) or SHAM surgery was performed on 17-day-old Sprague Dawley rats.
- Hippocampal and cortical tissues were collected at post-injury days (PID) 1, 2, 3, 5, 7, and 14.
- Immunoblotting was used to quantify 145 and 120 SBDP levels in ipsilateral and contralateral brain tissues.
Main Results:
- 145 SBDPs significantly increased in ipsilateral hippocampus and cortex within the first 3 PID, with more sustained elevations in the hippocampus.
- Contralateral tissue showed limited 145 SBDP changes, primarily in the cortex at PID2.
- 120 SBDPs showed minimal increases, observed only in the hippocampus at PID1 and cortex at PID2, contrary to expectations.
Conclusions:
- Early elevations of 145 SBDPs post-TBI in immature rats resemble adult patterns but resolve faster.
- The minimal increase in 120 SBDPs suggests that calpain-dependent cell death pathways are predominant over caspase-dependent pathways in the 17-day-old rat brain after CCI.
- Developmental stage significantly influences the cell death mechanisms activated by TBI.
Abstract:
After traumatic brain injury (TBI), proteolysis of Alpha II Spectrin by Calpain 1 produces 145 Spectrin breakdown products (SBDPs) 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.
