Susceptibility of hippocampal neurons to mechanically induced injury

Geddes, Donna M.; LaPlaca, Michelle C.; Cargill, Robert S.

doi:10.1016/s0014-4886(03)00254-1

Cited by 109 publications

(84 citation statements)

References 50 publications

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“…Previously, our laboratory has shown that neurons in the lateral neocortex show mechanoporation after diffuse TBI and that a subset of these mechanoporated neurons progress to necrotic change (Singleton and Povlishock, 2004;Farkas et al, 2006). These findings have been corroborated in vitro by the demonstration of membrane poration and ultimate neuronal death after mechanical injury (Geddes et al, 2003b;LaPlaca et al, 2009;Cullen et al, 2011), thereby reaffirming the importance of this membrane poration. Paralleling membrane perturbation is the occurrence of traumatically induced diffuse axonal injury; a pathology that contributes to posttraumatic morbidity and may be related to focal axolemmal mechanoporation (Singleton and Povlishock, 2004).…”

Section: Introductionmentioning

confidence: 68%

“…Both acute and chronic membrane perturbation have been shown to induce the influx of calcium ions both at the cell soma and at points of cytoskeletal disruption along the neurites (LaPlaca and Thibault, 1998;Geddes et al, 2003b). The intensity and duration of the mechanical force exerted on the cell is positively correlated to the degree of mechanoporation and the influx of calcium (Lusardi et al, 2004b).…”

Section: Discussionmentioning

confidence: 99%

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Increased Intracranial Pressure after Diffuse Traumatic Brain Injury Exacerbates Neuronal Somatic Membrane Poration but not Axonal Injury: Evidence for Primary Intracranial Pressure-Induced Neuronal Perturbation

Lafrenaye

McGinn

Povlishock

2012

J Cereb Blood Flow Metab

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Increased intracranial pressure (ICP) associated with traumatic brain injury (TBI) is linked to increased morbidity. Although our understanding of the pathobiology of TBI has expanded, questions remain regarding the specific neuronal somatic and axonal damaging consequences of elevated ICP, independent of its impact on cerebral perfusion pressure (CPP). To investigate this, Fischer rats were subjected to moderate TBI. Measurements of ICP revealed two distinct responses to injury. One population exhibited transient increases in ICP that returned to baseline levels acutely, while the other displayed persistent ICP elevation (>20 mm Hg). Utilizing these populations, the effect of elevated ICP on neuronal pathology associated with diffuse TBI was analyzed at 6 hours after TBI. No difference in axonal injury was observed, however, rats exhibiting persistently elevated ICP postinjury revealed a doubling of neurons with chronic membrane poration compared with rats exhibiting only transient increases in ICP. Elevated postinjury ICP was not associated with a concurrent increase in DNA damage; however, traditional histological assessments did reveal increased neuronal damage, potentially associated with redistribution of cathepsin-B from the lysosomal compartment into the cytosol. These findings indicate that persistently increased ICP, without deleterious alteration of CPP, exacerbates neuronal plasmalemmal perturbation that could precipitate persistent neuronal impairment and ultimate neuronal death.

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Section: Introductionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Increased Intracranial Pressure after Diffuse Traumatic Brain Injury Exacerbates Neuronal Somatic Membrane Poration but not Axonal Injury: Evidence for Primary Intracranial Pressure-Induced Neuronal Perturbation

Lafrenaye

McGinn

Povlishock

2012

J Cereb Blood Flow Metab

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“…Moreover, it was previously shown that after TBI the hippocampal neurons are extremely vulnerable, which may also underlie the differential effect of PD123319 on cognitive and motor function. 22 A growing body of evidence has linked AT 2 to learning and memory processes-e.g., findings that mice lacking the AT 2 gene have significantly impaired spatial memory performance. 23 Furthermore, AT 2 activation improved spatial memory, 23 and AT 2 was suggested to underlie the beneficial effects of angiotensin receptor type 1 blockers in memory impairment.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotection after Traumatic Brain Injury in Heat-Acclimated Mice Involves Induced Neurogenesis and Activation of Angiotensin Receptor Type 2 Signaling

Umschweif

Shabashov²,

Alexandrovich³

et al. 2014

J Cereb Blood Flow Metab

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Long-term exposure of mice to mild heat (341C±11C) confers neuroprotection against traumatic brain injury (TBI); however, the underling mechanisms are not fully understood. Heat acclimation (HA) increases hypothalamic angiotensin II receptor type 2 (AT 2 ) expression and hypothalamic neurogenesis. Accumulating data suggest that activation of the brain AT 2 receptor confers protection against several types of brain pathologies, including ischemia, a hallmark of the secondary injury occurring following TBI. As AT 2 activates the same pro-survival pathways involved in HA-mediated neuroprotection (e.g., Akt phosphorylation, hypoxia-inducible factor 1a (HIF-1a), and brain-derived neurotrophic factor (BDNF)), we examined the role of AT 2 in HA-mediated neuroprotection after TBI. Using an AT 2 -specific antagonist PD123319, we found that the improvements in motor and cognitive recovery as well as reduced lesion volume and neurogenesis seen in HA mice were all diminished by AT 2 inhibition, whereas no significant alternations were observed in control mice. We also found that nerve growth factor/tropomyosin-related kinase receptor A (TrkA), BDNF/TrkB, and HIF-1a pathways are upregulated by HA and inhibited on PD123319 administration, suggesting that these pathways play a role in AT 2 signaling in HA mice. In conclusion, AT 2 is involved in HA-mediated neuroprotection, and AT 2 activation may be protective and should be considered a novel drug target in the treatment of TBI patients.

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“…22 Disproportionate loss of hippocampal volume (in comparison with other deep central structures and cortical areas) is also consistent with a growing body of evidence from experimental literature suggesting profound cell loss or damage in the hippocampus following TBI. Geddes et al 23 found hippocampal neurons to be more susceptible to mechanically-induced trauma than cortical neurons, exhibiting greater intracellular free calcium concentration and sustained intracellular adenosine triphosphate deficits in a rodent study using a cell straining apparatus. Others have reported impaired long-term potentiation 24 fluid percussion injury in hippocampal tissue, despite no change in cortical tissue.…”

Section: Discussionmentioning

confidence: 99%

Hippocampus, amygdala, and basal ganglia morphometrics in children after moderate‐to‐severe traumatic brain injury

Wilde

Bigler

Hunter

et al. 2007

Develop Med Child Neuro

108

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While closed head injury frequently results in damage to the frontal and temporal lobes, damage to deep cortical structures, such as the hippocampus, amygdala, and basal ganglia, has also been reported. Five deep central structures (hippocampus, amygdala, globus pallidus, putamen, and caudate) were examined in 16 children (eight males, eight females; aged 9-16y), imaged 1 to 10 years after moderate-tosevere traumatic brain injury (TBI), and in 16 individuallymatched uninjured children. Analysis revealed significant volume loss in the hippocampus, amydala, and globus pallidus of the TBI group. Investigation of relative volume loss between these structures and against five cortical areas (ventromedial frontal, superomedial frontal, lateral frontal, temporal, and parieto-occipital) revealed the hippocampus to be the most vulnerable structure following TBI (i.e. greatest relative difference between the groups). In a separate analysis excluding children with focal hippocampal abnormalities (e.g. lesions), group differences in hippocampal volume were still evident, suggesting that hippocampal damage may be diffuse rather than focal.Although frontal and temporal areas have been considered most susceptible to focal injury following traumatic brain injury (TBI), deep central brain structures, such as the hippocampal/amygdalar complex and the basal ganglia, are also vulnerable to TBI-related injury. Structural neuroimaging studies of adult patients with TBI, using T 2 -weighted fast field echo (FFE), 1 T 2 -weighted 2 and susceptibility-weighted 3 gradient echo imaging pulse sequences, have recently identified increased evidence for diffuse axonal injury and 'microbleeds' in the basal ganglia and medial temporal lobes. Similarly, functional neuroimaging has implicated deep central areas, with evidence of long-term reduction in cerebral blood flow, 4 hypoperfusion, 5 and decreased cerebral metabolic rate 6 in the basal ganglia/striatum following TBI. Medial temporal lobe vulnerability is also suggested by positron emission tomography and single-photon emission computed tomography, 7 with an association between brain injuryinduced abnormalities and neurocognitive deficits. Finally, proton magnetic resonance spectroscopy has revealed a significantly decreased N-acetylaspartate/choline ratio in the basal ganglia and hippocampus of patients with TBI. 8 Quantitative magnetic resonance imaging (MRI) studies of adult patients with TBI have found hippocampal atrophy which correlated with injury severity as measured by the Glasgow Coma Scale score. 9-12 However, only three studies have examined hippocampal volume in individuals experiencing TBI as children or adolescents, [13][14][15] and only a single study has examined caudate volume in this population. 14 Despite growing evidence of injury to the amygdala and the basal ganglia from various mechanisms, there has been no examination of the amygdala, globus pallidus, or putamen using quantitative brain imaging in pediatric patients with TBI. This absence is notable, given that thes...

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Susceptibility of hippocampal neurons to mechanically induced injury

Cited by 109 publications

References 50 publications

Increased Intracranial Pressure after Diffuse Traumatic Brain Injury Exacerbates Neuronal Somatic Membrane Poration but not Axonal Injury: Evidence for Primary Intracranial Pressure-Induced Neuronal Perturbation

Increased Intracranial Pressure after Diffuse Traumatic Brain Injury Exacerbates Neuronal Somatic Membrane Poration but not Axonal Injury: Evidence for Primary Intracranial Pressure-Induced Neuronal Perturbation

Neuroprotection after Traumatic Brain Injury in Heat-Acclimated Mice Involves Induced Neurogenesis and Activation of Angiotensin Receptor Type 2 Signaling

Hippocampus, amygdala, and basal ganglia morphometrics in children after moderate‐to‐severe traumatic brain injury

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