Akinori Yagihashi

Apoptosis of auditory neurons following central process injury

Although apoptotic changes in auditory neurons induced by injury to peripheral processes (dendrites) have been intensively studied, apoptotic changes in auditory neurons induced by injury to central processes (axons of spiral ganglion cells, SGCs) have not been reported previously, probably due to lack of an experimental model. The present study reports for the first time the appearance, extent, and time course of SGC apoptosis following injury to the central processes. Apoptosis was studied in a rat model that consisted of compression of the auditory nerve in the cerebellopontine (CP) angle cistern with intraoperative recordings of auditory nerve compound action potentials (CAPs) to ensure highly reproducible results. Rats were killed between day 0 and day 14 after compression and apoptosis of SGCs was evaluated quantitatively as well as qualitatively by terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining, anti-activated caspase-3 immunostaining, Hoechst 33342 staining, and electron microscopy. The average number of TUNEL-positive apoptotic SGCs in each cochlear turn increased from day 1 to day 5 and then decreased gradually to an undetectable level on day 14 after compression. The average proportion of apoptotic SGCs identified in any cochlear turn on any day was always lower than 10%. The results of our present study should be useful in determining the therapeutic time window for rescuing auditory neurons undergoing apoptosis due to injury during surgery in the CP angle.

Macrophage colony stimulating factor (M-CSF) protects spiral ganglion neurons following auditory nerve injury: morphological and functional evidence

Because hearing disturbance due to auditory nerve dysfunction imposes a formidable burden on human beings, intense efforts have been expended in experimental and clinical studies to discover ways to restore normal hearing. However, the great majority of these investigations have focused on the peripheral process side of bipolar auditory neurons, and very few trials have focused on ways to halt degenerative processes in auditory neurons from the central process side (in the cerebellopontine angle). In the present study, we investigated whether administration of macrophage colony-stimulating factor (M-CSF) could protect auditory neurons in a rat model of nerve injury. The electrophysiological and morphological results of our study indicated that M-CSF could ameliorate both anterograde (Wallerian) and retrograde degeneration in both the CNS and PNS portions of the auditory nerve. We attribute the success of M-CSF therapy to the reported functional dichotomy (having the potential to cause both neuroprotective and neurotoxic effects) of microglia and macrophages. Whether the activities of microglia/macrophages are neuroprotective or neurotoxic may depend upon the nature of the stimulus that activates the cells. In the present study, the neuroprotective effects of M-CSF that were observed could have been due to M-CSF we administered and to M-CSF released from endothelial cells, resident cells of the CNS parenchyma, or infiltrating macrophages. Another possibility is that M-CSF ameliorated apoptotic auditory neuronal death, although this hypothesis remains to be proved in future studies.

A case of anaplastic pleomorphic xanthoastrocytoma presenting with tumor bleeding and cerebrospinal fluid dissemination

Pleomorphic xanthoastrocytoma (PXA) has been considered an astrocytic tumor with a relatively favorable prognosis. However, PXA cases having several recurrent patterns with poor prognosis have been reported in recent years, and a new concept of anaplastic PXA has been proposed. The present case was a 59-year-old woman who presented with tumor bleeding onset and cerebrospinal fluid dissemination. The patient had sudden-onset right hemiparesis, aphasia, and consciousness disturbance and was admitted to a local area hospital. After emergency surgery had removed the hematoma, postoperative contrast-enhanced CT scan revealed a left temporal tumor. A second surgery was therefore performed for initial tumor removal 2 months later. Histopathological findings showed that the tumor was typical PXA with strong pleomorphism and xanthomatous changes and contained an ependymoma-like component in the center area. However, endothelial proliferation and mitosis were more remarkable compared to ordinary PXA. The MIB-1 labeling index was 9.8% high. From these findings, the histopathological diagnosis was anaplastic PXA. The patient underwent surgery to remove recurrent tumors 5 and 16 months later. The patient died 36 months after the first onset, and CT revealed glioblastoma-like findings and cerebrospinal fluid dissemination. This case report is the first case in which PXA presented with tumor bleeding onset. Histopathological findings suggested anaplastic PXA from the first surgical specimens, and PXA recurred many times. We thus believe that the patient displayed primary anaplastic PXA rather than secondary anaplastic PXA that results in malignant transformation.

Nimodipine ameliorates trauma-induced cochlear neuronal death.

Abstract Excessive entry of Ca2+ into injured cochlear neurons activates various Ca2+ -activated enzymes and subsequent spiral ganglion cell death. Therefore, preventing intracellular calcium overload by using Ca2+ channel antagonists may become an important countermeasure to spiral ganglion cell death. We experimentally investigated whether an L-type Ca2+ channel blocker (nimodipine) can rescue traumatized cochlear neurons from degeneration. A group of rats (n = 6) was pre-operatively treated with nimodipine for one week and compression injury was applied to the cerebellopontine angle portion of the cochlear nerve in a highly quantitative fashion. The rats from the compression with nimodipine treatment groups were post-operatively treated with nimodipine for 10 days and killed for histological examination. The histological analysis of the temporal bones revealed that the spiral ganglion cells in the basal turn of the cochlea where the magnitude of traumatic impact had been the least in our experimental condition were rescued in a statistically significant fashion in the compression with nimodipine treatment group. The results of the present study indicate that nimodipine may become an intra- and post-operative important adjunct to raise the rate of hearing preservation in vestibular schwannoma excision or other cerebellopontine angle surgical interventions.

Displacement of central sulcus in cerebral arteriovenous malformation situated in the peri-motor cortex as assessed by magnetoencephalographic study

SummaryBackground. Intra-operative monitoring of the position of the central sulcus (CS) is indispensable to properly treat a peri-motor cortex lesion. Noninvasive preoperative studies for identification of CS are also needed for choosing the optimal operative procedure. Magneto-encephalography (MEG) has recently been introduced for non-invasive preoperative investigation and cortical functional mapping. Methods. Stereotactic mapping of functional CS anatomy was performed preoperatively on 13 subjects using somatosensory evoked fields with MRI-linked whole head MEG system. All subjects had a left sided peri-motor cortex lesion with diagnoses including the following conditions: three arteriovenous malformations (AVM), seven gliomas, three meningiomas. Findings. Functional CS in supratentorial brain tumor and parietal AVM cases corresponded with anatomical CS identified by MRI. But the AVM cases in whom the nidus was situated within the peri-motor cortex showed discrepancies between anatomical CS and functional CS. Interpretation. Careful consideration of the operative procedure combined with non-invasive cortical functional mapping is needed to optimally treat AVM and congenital brain lesions situated in the anatomical peri-motor cortex.

Trauma-induced hearing loss due to apoptotic auditory neuronal death in cerebellopontine angle manipulations: an experimental study

Abstract This study reports for the first time the appearance, extent and duration of auditory neuron apoptosis following injury to the central processes. Apoptosis was studied in a rat model that consisted of compression of the auditory nerve in the cerebellopontine angle cistern with intraoperative recordings of auditory nerve compound action potentials to ensure highly reproducible results. Rats were killed between days 0 and 14 after compression, and apoptosis of spiral ganglion cells (SGCs) was evaluated quantitatively and qualitatively. The average number of TUNEL-positive apoptotic SGCs in each cochlear turn increased from days 1 to 5, and then decreased gradually to an undetectable level on day 14 after compression. The average proportion of apoptotic SGCs identified in any cochlear turn on any day was always lower than 10%. These results of our present study should be useful in determining the therapeutic time window for rescuing auditory neurons undergoing apoptosis due to injury during surgery in the cerebellopontine angle.