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.
METHODS: Adult male rats were exposed to a single shot of
shock waves (produced by
silver azide explosion) at overpressures 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.
CONCLUSIONS: 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.