Katsuya Masui

Expression of c-Jun N-terminal kinases after axotomy in the dorsal motor nucleus of the vagus nerve and the hypoglossal nucleus

Abstract. c-Jun N-terminal kinases (JNKs)/stress-activated protein kinases (SAPKs) are a subgroup of mitogen-activated protein kinases (MAPKs), and important mediators of signal transduction from the cell surface to the nucleus. JNK phosphorylates the transcription factor c-Jun. c-Jun is one of the earliest and most consistent markers for neurons that respond to nerve-fiber transection. To elucidate the c-Jun metabolism after axotomy, we investigated the expression of JNKs mRNA and of JNKs and c-Jun proteins following vagus and hypoglossal nerve transection. We found that JNK 1, JNK 2 and JNK 3 mRNA were positive in the cytoplasm of neuronal and glial cells. JNK 1 and JNK 2 protein were distributed mainly in the cytoplasm of neurons and glial cells, while only JNK 3 immunoreactivity was observed intensely in the nuclei of neuronal cells. Activated JNK was also observed intensely in the nuclei of neuronal cells. In sham-operated animals, the cytoplasm of a few glial cells showed moderate immunoreactivity for activated JNK, while after axotomy the cytoplasm of all perineuronal microglial cells were stained intensely. Up-regulated c-Jun and phosphorylated c-Jun immunoreactivities were found in the nuclei of neuronal cells in the severed side of both the dorsal motor and hypoglossal nuclei. These results indicate that the principal activity of JNKs in neurons is contributed largely by JNK 3 under both normal and axotomized conditions, and that JNKs play an important role in signal transduction of perineuronal microglial cells after axotomy.

Changes in expression of p38 mitogen‐activated protein kinase in the dorsal motor nucleus of the vagus nerve and hypoglossal nucleus after axotomy in adult rats

Mitogen‐activated protein (MAP) kinase cascades are activated in response to various extracellular stimuli. P38 MAP kinase is one of the MAP kinase family and is activated by proinflammatory cytokines and environmental stresses. Activating transcription factor‐2 (ATF‐2) is one of the targets for p38 MAP kinase. To obtain information on the role of the p38 MAP kinase in the neurons and glial cells after axotomy, we investigated changes of expression of p38 MAP kinase, MAP kinase kinase (MKK) 3, MKK4, MKK6 and ATF‐2 in the dorsal motor nucleus of the vagus nerve and the hypoglossal nucleus following axotomy in rats using in situ hybridization and immunohistochemical techniques. Expression of p38 MAP kinase mRNA was observed in the neurons in control rats and showed no remarkable changes after axotomy in both nuclei. On the other hand, expression of p38 MAP kinase mRNA was observed in the perineuronal microglias after axotomy. The expression of p38 MAP kinase, activated p38 MAP kinase, MKK3 and ATF‐2 were immunohistochemically observed in neurons of control rats in both nuclei. After axotomy, the expression of p38 MAP kinase, active and inactive, and ATF‐2 in neurons were reduced in both nuclei, while expression of mRNA of p38 MAP kinase showed no reduction in neurons. These findings indicate that p38 MAP kinase is functionally regulated not by synthesis but by phosphorylation and regulates the activation of ATF‐2 in neurons, and this cascade plays some role in retrograde neuronal reactions. Moreover, perineuronal microglial cells showed strong expression of p38 MAP kinase, active and inactive, after axotomy in both nuclei. These findings suggest that p38 MAP kinase is related to microglial cell reactions after axotomy.

Relationship Between Clinical Features and T2-Weighted Magnetic Resonance Images in Symptomatic Rathke Cleft Cysts

BACKGROUND It is not known when surgery is appropriate for the treatment for incidental Rathke cleft cysts because knowledge of their natural history is lacking. In this study, we sought to determine whether symptomatic Rathke cleft cysts could be distinguished by their signal intensities in magnetic resonance (MR) images. We analyzed the relationship between these signal intensities and clinical manifestations of the cysts and their patterns of expansion. METHODS MR signal intensities on T1-weighted (T1W) and T2-weighted (T2W) images for 52 cases were categorized into 3 types. Type 1 (20 cases) showed low signal intensities on T1W images and hyperintensity on T2W images. Type 2 (10 cases) showed hyperintensity on both T1W and T2W images. Type 3 (22 cases) showed hypointensity on T2W images. RESULTS A significantly higher proportion of patients with type 1 signal intensities had large cysts compressing their third ventricle than patients with the other 2 types of signal intensities. Patients with type 1 signal intensities also frequently had visual disturbances. Anterior pituitary dysfunction was observed more often in patients with type 2 or 3 signal intensities than in patients with type 1 intensities. CONCLUSIONS We conclude that Rathke cleft cysts that show an MR signal intensity similar to that of cerebrospinal fluid grow slowly and are frequently diagnosed as cysts associated with visual disturbance when they become large. It may be possible to predict the clinical progression of Rathke cleft cysts by assessing MR signal intensities.

Pituitary Apoplexy Caused by Hemorrhage From Pituitary Metastatic Melanoma: Case Report

Melanoma metastases to the pituitary gland are extremely rare, with only a few reported cases. We report an unusual case of pituitary metastatic melanoma in which the patient presented with pituitary apoplexy. A 68-year-old man presented general fatigue and anorexia following sudden headache. Neurological examination disclosed bitemporalhemianopsia. Computed tomography (CT) scans revealed a suprasellar mass including intratumoral hematoma. Magnetic resonance (MR) images demonstrated a circumscribed mass lesion in the intra- and suprasellar regions, compressing the optic chiasm. Surgical exploration was performed through a transsphenoidal approach, and a mixture of tumor and necrotic tissue with old hematoma was obtained. The histological examination of the specimen revealed a partly necrotic, malignant tumor with focal melanotic pigmentation. Histopathologically, the diagnosis was consistent with pituitary apoplexy caused by hemorrhage from pituitary metastatic melanoma.

Transdural Indocyanine Green Videography for Superficial Temporal Artery–to–Middle Cerebral Artery Bypass—Technical Note

BACKGROUND Neurosurgical application of indocyanine green (ICG) videography before performing a dural opening, known as transdural ICG videography, has been used during surgery of meningiomas associated with venous sinuses as well as cranial and spinal arteriovenous malformations. However, its use for a superficial temporal artery (STA)-to-middle cerebral artery (MCA) bypass has not been reported. METHODS We performed a retrospective analysis of medical records of patients who underwent transdural ICG videography during STA-MCA bypass performed between January 2012 and March 2015. The primary outcome was visualization of recipient cortical arteries; secondary outcomes were surgical modifications and complications as well as any adverse events associated with transdural ICG videography. RESULTS We analyzed 29 STA-MCA bypass procedures performed in 30 hemispheres with atherosclerotic steno-occlusive disease and found that the proper recipient was identified in 28 hemispheres. Subsequently modified procedures for those were a tailored dural incision and craniotomy correction. No complications associated with ICG administration were encountered; during the postoperative course, transient aphasia was noted in 1 case, chronic subdural hematoma was noted in 1 case, and subdural effusion was noted in 2 cases. CONCLUSIONS Transdural ICG videography for atherosclerotic steno-occlusive disease facilitates modifications during STA-MCA bypass procedures. Recognition of the proper recipient cortical arteries before a dural incision allows the neurosurgeon to perform a tailored dural incision and extension of the bone window, although the contribution to surgical outcome has yet to be determined.