Defining the microanatomic differences between the human brain and that of other mammals is key to understanding its unique computational power. Although much effort has been devoted to comparative studies of neurons, astrocytes have received far less attention. We report here that protoplasmic astrocytes in human neocortex are 2.6-fold larger in diameter and extend 10-fold more GFAP (glial fibrillary acidic protein)-positive primary processes than their rodent counterparts. In cortical slices prepared from acutely resected surgical tissue, protoplasmic astrocytes propagate Ca 2ϩ waves with a speed of 36 m/s, approximately fourfold faster than rodent. Human astrocytes also transiently increase cystosolic Ca 2ϩ in response to glutamatergic and purinergic receptor agonists. The human neocortex also harbors several anatomically defined subclasses of astrocytes not represented in rodents. These include a population of astrocytes that reside in layers 5-6 and extend long fibers characterized by regularly spaced varicosities. Another specialized type of astrocyte, the interlaminar astrocyte, abundantly populates the superficial cortical layers and extends long processes without varicosities to cortical layers 3 and 4. Human fibrous astrocytes resemble their rodent counterpart but are larger in diameter. Thus, human cortical astrocytes are both larger, and structurally both more complex and more diverse, than those of rodents. On this basis, we posit that this astrocytic complexity has permitted the increased functional competence of the adult human brain.
An individual patient's risk for postoperative verbal memory decline following dominant or nondominant ATL can be predicted using clinical data routinely available preoperatively (side of surgery, qualitative MRI, baseline memory testing, IAP performance). This information may be useful for preoperative patient counseling.
The RTPZ and BMP pathways regulate the self-maintenance of adult human WMPCs, and can be modulated to induce their oligodendrocytic or astrocytic differentiation. As such, they provide targets by which to productively mobilize resident progenitor cells of the adult human brain.
Gangliogliomas are indolent neoplasms that are often associated with long-standing intractable seizures. The seizure-free outcome following ganglioglioma resection alone (or "lesionectomy") has been generally favorable, ranging in most series from 50% to 65%. Thus, the value of resection of epileptogenic cortex in addition to tumor with regard to seizure outcome has been the subject of controversy. The authors describe a series of 12 patients with frontal or temporal lobe gangliogliomas associated with long-standing intractable seizures. In these patients, intraoperative electrocorticography was used to guide the resection of epileptogenic cortex along with tumor. Functional brain mapping, interictal and ictal monitoring of seizures, as well as thorough neuropsychological assessments were performed prior to resection in all cases. Outcome with regard to seizures, tumor recurrence, and neurological deficits was assessed with a mean follow-up period of 3.1 years. There was universal freedom from seizures postoperatively in 11 patients in whom complete or near-complete resection of epileptogenic cortex was achieved. In one patient in whom complete tumor resection and subtotal removal of epileptogenic cortex was achieved, a 95% reduction in seizure frequency was identified. No tumor recurrence or neurological deficits were observed. In a subset of four patients, neuropsychological and cognitive function were evaluated pre- and postoperatively. In these four, a clear trend toward improvement was noted in most functions. Thus, resection of epileptogenic cortex along with tumor may improve seizure outcome in selected patients with tumor-associated epilepsy without engendering identifiable neurological or cognitive deficits attributable to the incremental resection.
Purpose: This retrospective study was done to better understand the conditions for which stereotactic radiosurgery (SRS) for glioblastoma may be efficacious.
Methods:Between 2000 and 2007, 33 patients with a pathological diagnosis of glioblastoma received SRS with the Novalis ® Shaped Beam Radiosurgery system. Eighteen patients (54%) underwent salvage SRS for recurrence while 15 (45%) patients received upfront SRS following standard fractionated RT for newly diagnosed glioblastoma.Results: There were no RTOG grade >2 acute side effects. The median survival after SRS was 6.7 months (range 1.4 -74.7). There was no significant difference in overall survival (from the time of initial diagnosis) with respect to the timing of SRS (p = 0.2). There was significantly better progression free survival in patients treated with SRS as consolidation versus at the time of recurrence (p = 0.04). The majority of patients failed within or at the margin of the SRS treatment volume (21/26 evaluable for recurrence).
Conclusion:SRS is well tolerated in the treatment of glioblastoma. As there was no difference in survival whether SRS is delivered upfront or at recurrence, the treatment for each patient should be individualized. Future studies are needed to identify patients most likely to respond to SRS.
The statins have been proposed as possible therapeutic agents for a variety of autoimmune disorders, including multiple sclerosis. In a genomic screen, we found that glial progenitor cells (GPCs) of the adult human white matter expressed significant levels of the principal statin target, HMG-CoA reductase, as well as additional downstream members of the sterol synthesis pathway. We therefore asked if statin treatment might influence the differentiated fate of adult glial progenitor cells. To assess the functional importance of the sterol synthesis pathway to adult human glial progenitors, we used simvastatin or pravastatin to inhibit HMG-CoA reductase, and then assessed the phenotypic differentiation of the progenitors, as well as the molecular concomitants thereof. We found that both statins induced a dose-dependent induction of oligodendrocyte phenotype, and concomitant reduction in progenitor number. Oligodendrocyte commitment was associated with induction of the sterol-regulated nuclear co-receptor PPARgamma, and could be blocked by the specific PPARgamma antagonist GW9662. Thus, statins may promote oligodendrocyte lineage commitment by parenchymal glial progenitor cells; this might reduce the available progenitor pool, and hence degrade the long-term regenerative competence of the adult white matter.
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