Mechanoporation induced by diffuse traumatic brain injury: An irreversible or reversible response to injury?

被引:125
作者
Farkas, O
Lifshitz, J
Povlishock, JT
机构
[1] Virginia Commonwealth Univ, Dept Anat & Neurobiol, Richmond, VA 23298 USA
[2] Univ Pecs, Fac Med, Dept Neurosurg, H-7623 Pecs, Hungary
关键词
diffuse traumatic brain injury; neuron; dextrans; membrane disruption; membrane resealing; calpain;
D O I
10.1523/JNEUROSCI.5119-05.2006
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Diffuse traumatic brain injury (DTBI) is associated with neuronal plasmalemmal disruption, leading to either necrosis or reactive change without cell death. This study examined whether enduring membrane perturbation consistently occurs, leading to cell death, or if there is the potential for transient perturbation followed by resealing/recovery. We also examined the relationship of these events to calpain-mediated spectrin proteolysis (CMSP). To assess plasmalemmal disruption, rats ( n = 21) received intracerebroventricular infusion 2 h before DTBI of a normally excluded 10 kDa fluorophore-labeled dextran. To reveal plasmalemmal resealing or enduring disruption, rats were infused with another labeled dextran 2 h ( n = 10) or 6 h ( n = 11) after injury. Immunohistochemistry for the 150 kDa spectrin breakdown product evaluated the concomitant role of CMSP. Neocortical neurons were followed with confocal and electron microscopy. After DTBI at 4 and 8 h, 55% of all tracer-flooded neurons contained both dextrans, demonstrating enduring plasmalemmal leakage, with many demonstrating necrosis. At 4 h, 12.0% and at 8 h, 15.7% of the dual tracer-flooded neurons showed CMSP, yet, these demonstrated less advanced cellular change. At 4 h, 39.0% and at 8 h, 24.4% of all tracer-flooded neurons revealed only preinjury dextran uptake, consistent with membrane resealing, whereas 7.6 and 11.1%, respectively, showed CMSP. At 4 h, 35% and at 8 h, 33% of neurons demonstrated CMSP without dextran flooding. At 4 h, 5.5% and at 8 h, 20.9% of tracer-flooded neurons revealed only postinjury dextran uptake, consistent with delayed membrane perturbation, with 55.0 and 35.4%, respectively, showing CMSP. These studies illustrate that DTBI evokes evolving plasmalemmal changes that highlight mechanical and potential secondary events in membrane poration.
引用
收藏
页码:3130 / 3140
页数:11
相关论文
共 71 条
[51]   Traumatic axonal injury results in biphasic calpain activation and retrograde transport impairment in mice [J].
Saatman, KE ;
Abai, B ;
Grosvenor, T ;
Vorwerk, CK ;
Smith, DH ;
Meaney, DF .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2003, 23 (01) :34-42
[52]   Prolonged calpain-mediated spectrin breakdown occurs regionally following experimental brain injury in the rat [J].
Saatman, KE ;
BozyczkoCoyne, D ;
Marcy, V ;
Siman, R ;
McIntosh, TK .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 1996, 55 (07) :850-860
[53]  
SAIDO TC, 1993, J BIOL CHEM, V268, P25239
[54]   Dimethylsulfoxide enhances CNS neuronal plasma membrane resealing after injury in low temperature or low calcium [J].
Shi, R ;
Qiao, X ;
Emerson, N ;
Malcom, A .
JOURNAL OF NEUROCYTOLOGY, 2001, 30 (9-10) :829-839
[55]   Temperature dependence of membrane sealing following transection in mammalian spinal cord axons [J].
Shi, R ;
Pryor, JD .
NEUROSCIENCE, 2000, 98 (01) :157-166
[56]   Control of membrane sealing in injured mammalian spinal cord axons [J].
Shi, RY ;
Asano, T ;
Vining, NC ;
Blight, AR .
JOURNAL OF NEUROPHYSIOLOGY, 2000, 84 (04) :1763-1769
[57]  
SIMAN R, 1989, J NEUROSCI, V9, P1579
[58]   Identification and characterization of heterogeneous neuronal injury and death in regions of diffuse brain injury: Evidence for multiple independent injury phenotypes [J].
Singleton, RH ;
Povlishock, JT .
JOURNAL OF NEUROSCIENCE, 2004, 24 (14) :3543-3553
[59]   Traumatically induced axotomy adjacent to the soma does not result in acute neuronal death [J].
Singleton, RH ;
Zhu, JP ;
Stone, JR ;
Povlishock, JT .
JOURNAL OF NEUROSCIENCE, 2002, 22 (03) :791-802
[60]   CELL-MEMBRANE RESEALING BY A VESICULAR MECHANISM SIMILAR TO NEUROTRANSMITTER RELEASE [J].
STEINHARDT, RA ;
BI, GQ ;
ALDERTON, JM .
SCIENCE, 1994, 263 (5145) :390-393