Alpha-II-Spectrin after Controlled Cortical Impact in the Immature Rat Brain

Aikman, Jada M.; O'Steen, Barbara E.; Silver, X.; Torres, Raquel; Boslaugh, Sarah; Blackband, Stephen J.; Padgett, Kyle R.; Wang, Kevin; Hayes, Ronald L.; Pineda, José

doi:10.1159/000094171

Cited by 33 publications

(24 citation statements)

References 160 publications

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“…Aikman et al measured 150, 145 and 120 SBDPs in the cortex ipsilateral to injury during the first three days after controlled cortical impact (CCI) in the 9 day old rat (Aikman et al, 2006). To our knowledge, SBDP levels in other brain regions or beyond the first three days after experimental TBI in the immature brain have not been reported.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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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.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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“…Both calpain- (SBDP145 and 150) and caspase-3-mediated (SBDP120) SBDPs have been shown to increase in brain parenchyma following controlled cortical impact in mature and immature rodents and are readily detectable in cerebrospinal fluid (CSF) following injury (5, 6). In adults with traumatic brain injury (TBI), levels of SBDP120, 145, and 150 increase in CSF over time and have been shown to correlate with severity of injury and neurologic outcome (7, 8).…”

mentioning

confidence: 99%

Detection of Alpha II-Spectrin Breakdown Products in the Serum of Neonates With Congenital Heart Disease*

Jain¹,

Spaeder²,

Donofrio³

et al. 2014

Pediatric Critical Care Medicine

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Objectives To determine if alpha II-spectrin breakdown products can be detected in the serum of neonates with congenital heart disease in the perioperative period. Design Prospective observational cohort study. Setting Pediatric cardiac ICU in an urban tertiary care academic center. Patients Neonates with congenital heart disease undergoing surgical repair or palliation. Interventions Serial blood sampling for measurement of 120 and 150 kDa spectrin breakdown products. Measurements and Main Results Fourteen neonates with congenital heart disease undergoing cardiac surgery were evaluated. Nine infants underwent open-heart surgery and five underwent closed-heart surgery. Serum spectrin breakdown products were measured with sandwich enzyme-linked immunosorbent assay preoperatively and then 6, 24, 48, 72, and 96 hours following surgery. Brain imaging was obtained as part of routine clinical care in 12 patients pre-operatively and six patients postoperatively. Six patients had normal preoperative imaging (three closed-heart surgery and three open-heart surgery), whereas six had evidence of neurologic injury prior to surgery (one closed-heart surgery and five open-heart surgery). Only one patient had a postoperative imaging study that lacked injury. All others demonstrated infarction or hemorrhage. Spectrin breakdown product 120 kDa significantly increased 24 hours after open-heart surgery compared to preoperative values and time-matched closed-heart surgery levels. Spectrin breakdown product 150 kDa significantly increased 6 hours after open-heart surgery compared to preoperative values. There was no significant change in spectrin breakdown products following closed-heart surgery. Peak spectrin breakdown products significantly increased following open-heart surgery compared to closed-heart surgery. Conclusions Spectrin breakdown products can be detected in the serum of neonates with congenital heart disease in the perioperative period and levels increased to a greater degree in infants following open-heart surgery. These findings suggest that, in future work, serum spectrin breakdown products may potentially be developed as biomarkers for brain necrosis and apoptosis in infants with congenital heart disease.

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“…Brain & NeuroRehabilitation were found to increase significantly from 3 to 24 hours after brain injury [69,70]. The SBDP concentrations in the CSF are associated with mortality after brain injury [67].…”

Section: Biomarker In Mild Traumatic Brain Injurymentioning

confidence: 99%

Current State and Prospects of Development of Blood-based Biomarkers for Mild Traumatic Brain Injury

Lee

Seo

et al. 2017

Brain Neurorehabil

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Highlights• There are many unresolved clinical problems about mild traumatic brain injury (mTBI) such as a low sensitivity of standard neuroimaging studies, and absence of reliable predicting models.• It is very difficult to diagnose mTBI in symptomatic patients in the absence of witnesses, clear signs of head trauma, and abnormalities on neuroimaging.• Blood proteins have great potential as diagnostic and prognostic biomarkers of mTBI.• Technological advances in the targeted proteomics are expected to realize the clinical potential of blood-based protein biomarkers. ABSTRACTThe current understanding of the pathophysiology of mild traumatic brain injury (mTBI) is, without doubt, incomplete. Nevertheless, we tried to summarize the state-of-the-art explanation of how the brain is continuously injured even after a single impact. We also reviewed the real struggle of diagnosing mTBI, which culminated in showing the potential of blood-based biomarkers as an alternative or complementary way to overcome this difficulty. Pathophysiology of mTBI is subdivided into primary and secondary injuries. Primary injury is caused by a direct impact on the head and brain. Secondary injury refers to the changes in energy metabolism and protein synthesis/degradation resulting from the biochemical cascades as follows; calcium influx, mitochondrial dysfunction, fractured microtubules, and Wallerian degeneration, neuroinflammation, and toxic proteinopathy. Since the diagnosis of mTBI is made through the initial clinical information, it is difficult and inaccurate to diagnose mTBI without the absence of a witness or sign of head trauma. Blood-based biomarkers are expected to play an important role in diagnosing mTBI and predicting functional outcomes, due to their feasibility and the recent progress of targeted proteomics techniques (i.e., liquid chromatography tandem mass spectrometry [LC-MS/MS]).

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Alpha-II-Spectrin after Controlled Cortical Impact in the Immature Rat Brain

Cited by 33 publications

References 160 publications

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

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

Detection of Alpha II-Spectrin Breakdown Products in the Serum of Neonates With Congenital Heart Disease*

Current State and Prospects of Development of Blood-based Biomarkers for Mild Traumatic Brain Injury

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