Shock waves have been experimentally applied to various neurosurgical treatments including fragmentation of cerebral emboli, perforation of cyst walls or tissue, and delivery of drugs into cells. Nevertheless, the application of shock waves to clinical neurosurgery remains challenging because the threshold for shock wave–induced brain injury has not been determined. The authors investigated the pressure-dependent effect of shock waves on histological changes of rat brain, focusing especially on apoptosis.
Adult male rats were exposed to a single shot of shock waves (produced by silver azide explosion) at over-pressures of 1 or 10 MPa after craniotomy. Histological changes were evaluated sequentially by H & E staining and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling (TUNEL). The expression of active caspase-3 and the effect of the nonselective caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK) were examined to evaluate the contribution of a caspase-dependent pathway to shock wave–induced brain injury.
High-overpressure (> 10 MPa) shock wave exposure resulted in contusional hemorrhage associated with a significant increase in TUNEL-positive neurons exhibiting chromatin condensation, nuclear segmentation, and apoptotic bodies. The maximum increase was seen at 24 hours after shock wave application. Low-overpressure (1 MPa) shock wave exposure resulted in spindle-shaped changes in neurons and elongation of nuclei without marked neuronal injury. The administration of Z-VAD-FMK significantly reduced the number of TUNEL-positive cells observed 24 hours after high-overpressure shock wave exposure (p < 0.01). A significant increase in the cytosolic expression of active caspase-3 was evident 24 hours after high-overpressure shock wave application; this increase was prevented by Z-VAD-FMK administration. Double immunofluorescence staining showed that TUNEL-positive cells were exclusively neurons.
The threshold for shock wave–induced brain injury is speculated to be under 1 MPa, a level that is lower than the threshold for other organs. High-overpressure shock wave exposure results in brain injury, including neuronal apoptosis mediated by a caspase-dependent pathway. This is the first report in which the pressure-dependent effect of shock wave on the histological characteristics of brain tissue is demonstrated.
Address reprint requests to: Miki Fujimura, M.D., Ph.D., Department of Neurosurgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. email:
BayarNKaymazFFApanAYilmazECakarAN: Effects of electrohydraulic extracorporeal shock wave lithotripsy on submandibular gland in the rat: electron microscopic evaluation. Int J Pediatr Otorhinolaryngol63:223–2332002
ChenJJinKChenMPeiWKawaguchiKGreenbergDA: Early detection of DNA strand breaks in the brain after transient focal ischemia: implications for the role of DNA damage in apoptosis and neuronal cell death. J Neurochem69:232–2451997
CzurkoATothZDocziTGallyasF: Intracranial pressure waves generated by high-energy short laser pulses can cause morphological damage in remote areas: comparison of the effects of 2.1-micron Ho:YAG and 1.06-micron Nd:YAG laser irradiations in the rat brain. Lasers Surg Med21:444–4551997
FujimuraMMorita-FujimuraYKawaseMCopinJCCalaguiBEpsteinCJ: Manganese superoxide dismutase mediates the early release of mitochondrial cytochrome C and subsequent DNA fragmentation after permanent focal cerebral ischemia in mice. J Neurosci19:3414–34221999
HaraHFriedlanderRMGagliardiniVAyataCFinkKHuangZ: Inhibition of interleukin 1β converting enzyme family proteases reduces ischemic and excitoxic neuronal damage. Proc Natl Acad Sci U S A94:2007–20121997
LudwigHCBauerCFuhrbergPTeichmannHHBirbilisTMarkakisE: Optimized evaluation of a pulsed 2.09 microns holmium:YAG laser impact on the rat brain and 3 D-histomorphometry of the collateral damage. Minim Invasive Neurosurg41:217–2221998
Morita-FujimuraYFujimuraMKawaseMMurakamiKKimGWChanPH: Inhibition of interleukin-1beta converting enzyme family proteases (caspases) reduces cold injury-induced brain trauma and DNA fragmentation in mice. J Cereb Blood Flow Metab19:634–6421999
NakagawaASatoJHiranoTOhkiTSaitoTTakayamaK: Osteopromotion for cranioplasty using shock wave. Experiment using skull defect animal model. Proceedings of the 24th International Symposium Shock Waves (ISSW 24)Beijing, ChinaCD-ROM No. 27992004
TavakkoliJBirerAArefievAPratFChapelonJYCathignolD: A piezocomposite shock wave generator with electronic focusing capability: application for producing cavitation-induced lesions in rabbit liver. Ultrasound Med Biol23:107–1151997
WangCJWangFSHuangCCYangKDWengLHHuangHY: Treatment for osteonecrosis of the femoral head: comparison of extracorporeal shock waves with core decompression and bone-grafting. J Bone Joint Surg Am87:2380–23872005