Imaging mass spectrometry detects dynamic changes of phosphatidylcholine in rat hippocampal CA1 after transient global ischemia.

BACKGROUND AND PURPOSE: The initial steps in the cascade leading to cell death are still unknown because of the limitations of the existing methodology, strategy, and modalities used. METHODS: Imaging mass spectrometry (IMS) was used to measure dynamic molecular changes of phosphatidylcholine (PC) species in the rat hippocampus after transient global ischemia (TGI) for 6min. Fresh frozen sections were obtained after euthanizing the rats on Days 1, 2, 4, 7, 10, 14, and 21. Histopathology and IMS of adjacent sections compared morphological and molecular changes, respectively. RESULTS: Histopathological changes were absent immediately after TGI (at Day 1, superacute phase). At Days 2-21 after TGI (from subacute to chronic phases), histopathology revealed neuronal death associated with gliosis, inflammation, and accumulation of activated microglia in CA1. IMS detected significant molecular changes after TGI in the same CA1 domain: increase of PC (diacyl-16:0/22:6) in the superacute phase and increase of PC (diacyl-16:0/18:1) in the subacute to chronic phases. CONCLUSIONS: Histopathology and IMS can provide comprehensive and complementary information on cell death mechanisms in the hippocampal CA1 after global ischemia. IMS provided novel data on molecular changes in phospholipids immediately after TGI. Increased level of PC (diacyl-16:0/22:6) in the pyramidal cell layer of hippocampal CA1 prior to the histopathological change may represent an early step in delayed neuronal death mechanisms.

Transcription factor expression and Notch-dependent regulation of neural progenitors in the adult rat spinal cord.

Recent studies have demonstrated that neural stem cells and other progenitors are present in the adult CNS. Details of their properties, however, remain poorly understood. Here we examined the properties and control mechanisms of neural progenitors in the adult rat spinal cord at the molecular level. Adult and embryonic progenitors commonly expressed various homeodomain-type (Pax6, Pax7, Nkx2.2, and Prox1) and basic helix-loop-helix (bHLH)-type (Ngn2, Mash1, NeuroD1, and Olig2) transcriptional regulatory factors in vitro. Unlike their embryonic counterparts, however, adult progenitors could not generate specific neurons that expressed markers appropriate for spinal motoneurons or interneurons, including Islet1, Lim1, Lim3, and HB9. Cells expressing the homeodomain factors Pax6, Pax7, and Nkx2.2 also emerged in vivo in response to injury and were distributed in unique patterns in the lesioned spinal cord. However, neither the expression of the neurogenic bHLH factors including Ngn2, Mash1, and NeuroD1 nor subsequent generation of new neurons could be detected in injured tissue. Our results suggest that signaling through the cell-surface receptor Notch is involved in this restriction. The expression of Notch1 in vivo was enhanced in response to injury. Furthermore, activation of Notch signaling in vitro inhibited differentiation of adult progenitors, whereas attenuation of Notch signals and forced expression of Ngn2 significantly enhanced neurogenesis. These results suggest that both the intrinsic properties of adult progenitors and local environmental signals, including Notch signaling, account for the limited regenerative potential of the adult spinal cord.

Clinicopathological study of intracranial fusiform and dolichoectatic aneurysms : insight on the mechanism of growth.

BACKGROUND AND PURPOSE: Intracranial fusiform aneurysms can be divided into 2 clinically different subtypes: acute dissecting aneurysms and chronic fusiform or dolichoectatic aneurysms. Of these 2, the natural history and growth mechanism of chronic fusiform aneurysms remains unknown. METHODS: A consecutive series of 16 patients with chronic fusiform aneurysms was studied retrospectively to clarify patient clinical and neuroradiological features. Aneurysm tissues were obtained from 8 cases and were examined to identify histological features that could correspond to the radiological findings. RESULTS: Four histological features were found: (1) fragmentation of internal elastic lamina (IEL), (2) neoangiogenesis within the thickened intima, (3) intramural hemorrhage (IMH) and thrombus formation, and (4) repetitive intramural hemorrhages from the newly formed vessels within thrombus. IEL fragmentation was found in all cases, which suggests that this change may be one of the earliest processes of aneurysm formation. MRI or CT detected IMH, and marked contrast enhancement of the inside of the aneurysm wall (CEI) on MRI corresponded well with intimal thickening. Eight of 9 symptomatic cases but none of 7 asymptomatic cases presented with both radiological features. CONCLUSIONS: Data suggest that chronic fusiform aneurysms are progressive lesions that start with IEL fragmentation. Formation of IMH seems to be a critical event necessary for lesions to become symptomatic and progress, and this can be monitored on MRI. Knowledge of this possible mechanism of progression and corresponding MRI characteristics could help determine timing of surgical intervention.

New aneurysm clip and applier for narrow spaces: technical note.

OBJECTIVE: Aneurysm surgery carries considerable risk to the patient, in part because the surgical field can be so constricted that accurate placement of the aneurysm clip is impeded. In fact, most aneurysm clip appliers are so bulky that they can impair the surgeon's view, if the field is tight. We describe a system of aneurysm clips and appliers that have a very low profile and consequently allow better visualization of the operative field at critical moments during surgery. INSTRUMENTATION: A new system of clips for aneurysm surgery was developed to overcome some of the deficiencies of conventional sets. The new clip blades are opened from inside the spring, so the clip blades are clearly seen as they are applied across the base of the aneurysm. In addition, these clips can be angled in any desired direction in the applier, which makes their application easier. A third advantage is that the clip applier is used as a clip remover should adjustment or reapplication of the clip be necessary. RESULTS: Thirty aneurysms were obliterated with the new clips without any complications attributable to the clips. The new instruments allowed the safe application of clips to aneurysms in deep, confined, and anatomically complex spaces, such as aneurysms of the basilar tip and anterior communicating artery. CONCLUSION: The newly described system of aneurysm clips and appliers appears to have significant advantages over other currently available systems.

Persistent patent pseudolumen of ruptured dissecting aneurysm involving the posterior inferior cerebellar artery after proximal clipping.

In the majority of cases of ruptured vertebral artery dissecting aneurysm after proximal clipping, the dissected pseudolumen persists for a very short time, probably because re-entry from the pseudolumen is minimal. Recent reports have indicated a high risk of rebleeding of dissecting aneurysms involving the posterior inferior cerebellar artery (PICA) after proximal clipping, probably due to excessive retrograde flow from the distal vertebral artery into both the PICA and the pseudolumen. We describe an extremely rare case of ruptured dissecting aneurysm involving the PICA with persistent patent pseudolumen after proximal clipping. The present case was assumed to have developed a moderate retrograde flow just sufficient to maintain the patent pseudolumen in the chronic stage. Neointimal formation is suggested to be a possible mechanism by which the pseudolumen is stabilized for a very long period.

Basilar artery occlusion due to spontaneous basilar artery dissection in a child.

Basilar artery occlusion (BAO) causing brainstem infarction occurred in a 7-year-old boy without any basic disorders. A diagnosis of BAO due to basilar artery dissection (BAD) was suspected at angiography, and this was confirmed by gadolinium-enhanced magnetic resonance imaging (MRI). These investigations clearly showed all the typical diagnostic signs such as a pseudolumen, double lumen and intimal flap, and a pseudolumen in resolution. The spontaneous healing of the dissection was clearly demonstrated during 10 months of follow-up. We stress that BAD can occur in young children and that combined diagnosis with gadolinium-enhanced MRI and angiography is conclusive for diagnosis of dissecting aneurysms. Wider use of these combined diagnostic methods will allow the detection of less severe basilar artery dissection, thus extending the spectrum of presentation and prognosis.

Ruptured dissecting aneurysm as a cause of subarachnoid hemorrhage of unverified etiology.

BACKGROUND AND PURPOSE: The clinical features of "aneurysmal" subarachnoid hemorrhage (SAH) of angiographically unverified etiology were reviewed to clarify the incidence and natural history of dissecting aneurysms as the hemorrhagic source of SAH. METHODS: We reviewed 30 patients with SAH of unverified etiology in whom initial CT scan showed a diffuse or anteriorly distributed subarachnoid blood clot. Ten of the patients had stenotic or occlusive lesions (SOCL) on initial angiography, and these were the main focus of this study. RESULTS: Among the 10 patients with SOCL on initial angiography, the lesions were located on the anterior circulation in 6 and on the posterior circulation in 4. Ruptured dissecting aneurysms were confirmed by exploratory surgery or autopsy in 6 patients. Subsequent rupture occurred in 6 of the 10 patients (60%), and all 6 of these patients died as a result. CONCLUSIONS: The incidence (6/30) of dissecting aneurysms as the cause of SAH of unverified etiology was unexpectedly high, especially when initial angiography disclosed SOCL (6/10). The moribund patients with SOCL showed a high rate of rebleeding, and the untreated recurrent hemorrhages were fatal. Further MRI study is indicated for these patients to demonstrate the intramural hematoma. Compared with the devastating mortality caused by the subsequent ruptures, the extent of surgical morbidity was minor. Surgical intervention could therefore be justified when the following neuroradiological findings are present: (1) SOCL evident on angiography, (2) distribution of SAH on CT compatible with the location of the SOCL, and (3) intramural hematoma on MRI in the same region as the SOCL.

Primary cavernous sinus malignant lymphoma treated by gamma knife radiosurgery: case report and review of the literature.

BACKGROUND: Malignant lymphomas originating primarily in the cavernous sinus have not been histologically verified by any authors. The first reported case to our knowledge of primary cavernous sinus malignant lymphoma, initially diagnosed as benign meningioma and treated by gamma knife radiosurgery, is presented. CASE DESCRIPTION: The patient was a 77-year-old man whose initial symptoms were left facial hypesthesia and diplopia on left gaze. During the 21-month follow-up period after gamma knife radiosurgery, no evidence of tumor regrowth was seen in the irradiated area, but an unirradiated mass expanded with invasion of the brain stem. Subsequent surgery provided histologic verification of the diagnosis. Despite successful local tumor control, the patient died due to sepsis 31 months after the onset of symptoms. Autopsy failed to disclose any remaining lymphoma cells either in the primary lesion or anywhere throughout the entire body. CONCLUSION: Primary cavernous sinus malignant lymphoma is an extremely rare brain tumor, but it must be considered in the differential diagnosis of an enhanced mass in the cavernous sinus. Stereotactic radiosurgery using the gamma knife technique for intracranial brain tumors, especially in the cavernous sinus, is associated with risk, as was seen in our patient. Our experience points out the pitfalls of gamma knife radiosurgery; it should be performed only after histologic confirmation has been obtained.