Webster H. Pilcher

Uniquely hominid features of adult human astrocytes.

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 Ca2+ waves with a speed of 36 μm/s, approximately fourfold faster than rodent. Human astrocytes also transiently increase cystosolic Ca2+ 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.

Predicting verbal memory decline following anterior temporal lobectomy (ATL)

Objective: To develop a multivariate risk factor model for predicting postoperative verbal memory decline in an individual patient following dominant or nondominant anterior temporal lobectomy (ATL). Methods: The authors studied 132 consecutive ATL patients who 1) were older than 16 years at surgery, 2) had estimated preoperative Full Scale IQ score of >69, 3) had unilateral language dominance based on the intracarotid amobarbital procedure (IAP), and 4) underwent neuropsychological testing at baseline and ≥6 months postoperatively (mean 1.2 years). Five potential risk factors for postoperative verbal memory decline were selected a priori that reflect the functional adequacy of the to-be-resected temporal lobe. These were 1) resection in the dominant hemisphere, 2) MRI findings other than exclusively unilateral mesial temporal sclerosis, intact preoperative 3) immediate and 4) delayed verbal memory function, and 5) intact IAP memory performance following injection contralateral to the seizure focus. Verbal memory decline was defined using two verbal memory tests and published reliable change indices. Results: Thirty-eight percent of the sample declined reliably on one or both verbal memory measures. Logistic regression analysis demonstrated that all five risk factors were significantly and independently associated with outcome, with side of surgery having the strongest association (p < 0.0001) and preoperative immediate verbal memory the weakest (p < 0.05). Conclusions: 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.

Immunocytochemical localization of ACTH perikarya in nucleus tractus solitarius: evidence for a second opiocortin neuronal system

Immunocytochemical localization of ACTH-opiocortin perikarya was demonstrated in the medulla of colchicine-treated rat. Neuronal cell bodies and fibers containing ACTH-immunoreactivity were abundant in the caudal region of the nucleus tractus solitarius, specifically within pars commisuralis. Location of these opiocortin neurons within the nucleus tractus solitarius provides additional evidence for a role of these peptides in cardiovascular functions.

Complementary patterns of gene expression by human oligodendrocyte progenitors and their environment predict determinants of progenitor maintenance and differentiation

Glial progenitor cells are abundant in adult human white matter. This study was designed to identify signaling pathways regulating their self‐renewal and fate.

Resection of intrinsic tumors from nondominant face motor cortex using stimulation mapping: Report of two cases ☆

We report two right-handed patients who underwent resection of intrinsic glial tumors from the nondominant hemisphere, face motor cortex. Both patients underwent preoperative assessment with computed tomography and magnetic resonance imaging localizing the tumor in the inferior region of the Rolandic cortex. With the patients under general anesthesia and without muscular paralysis, the tumor volume was determined by intraoperative ultrasound and resective surgery accomplished with the aid of cortical and subcortical stimulation mapping techniques. Radical resection of the tumor from the face motor cortex was achieved in both patients. A transient contralateral facial weakness and apraxia were noted in each patient, and this resolved within 6 to 8 weeks following surgery. Removal of intrinsic tumors involving the nondominant face motor cortex may be safely achieved using brain mapping techniques to localize inferior Rolandic cortex and avoid resection of the hand motor cortex and descending subcortical motor pathways. Permanent disability will be prevented due to the bilateral representation of face motor function at the neocortical level. However, due to language localization in cortical zones contiguous with the dominant hemisphere, face motor cortex, we do not recommend resection of this region.

Stereotactic radiosurgery for glioblastoma: retrospective analysis

PurposeThis retrospective study was done to better understand the conditions for which stereotactic radiosurgery (SRS) for glioblastoma may be efficacious.MethodsBetween 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.ResultsThere 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).ConclusionSRS 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.

Co-localization of CRF-ir perikarya and ACTH-ir fibers in rat brain

The distribution of corticotropin-releasing factor immunoreactive (CRF-ir) perikarya and ACTH-ir fibers was examined immunocytochemically, in adjacent sections, in the forebrain and brainstem of the rat. Throughout the nervous system, a remarkable concordance of localization of these neuropeptide systems was noted. Both ACTH-ir fibers and CRF-ir perikarya were conjointly distributed within discrete hypothalamic, limbic and brainstem/autonomic regions previously demonstrated to contain opiate receptors and opiocortin (beta-endorphin, beta-LPH, ACTH) fibers. In view of the demonstrated interactions of CRF with the peripheral (pituitary) opiocortin system, these data suggest the possibility of a similar relationship of CRF and opiocortin systems in the central nervous system as well.

Fibro-osseous lesions of the central nervous system: Report of four cases and literature review

Fibro-osseous lesions, also reported as calcifying pseudoneoplasms of the neural axis, are uncommon lesions of the CNS. We report four additional cases: two extraaxial and two intraaxial, in patients ages 33, 47, 49, and 59 years at presentation. Fibro-osseous lesions involving the CNS demonstrate variable proportions of fibrous stroma, bone, palisading spindle to epithelioid to multinucleated cells in association with a highly distinctive, perhaps pathognomonic, chondromyxoid-like matrix often distributed in a nodular pattern. This histopathologically distinctive lesion can be seen in many regions of the neuraxis, often with a dural association, and most commonly along the vertebral column. It appears to be a slow-growing lesion and, with wide excision, the prognosis is excellent. The etiology remains unclear, but the preponderance of data favors a reactive rather than neoplastic process. If this putative pseudotumor is not recognized histopathologically, a neoplastic or infectious differential might result in inappropriate investigations and potentially harmful therapies.

Nuclear factor-κB in rat brain: Enhanced DNA-binding activity following convulsant-induced seizures

The DNA-binding protein nuclear factor-kappa B (NF-kappa B) is a pleiotropic transcription factor which regulates the transcription of specific target genes such as cytokines. The existence of NF-kappa B has not been reported in brain tissue. This is the first report demonstrating the expression of NF-kappa B in the rat brain. After pentylene tetrazole (s.c.)-induced clonic-tonic seizures at an LD50 dose of 85 mg/kg, we have shown a gradual increase in NF-kappa B expression reaching a maximum at 24 h, a decrease at 48 h and again increased at 96 and 120 h. A similar time-dependent pattern was observed for the NF-kappa B subunit p50 expression. The NF-kappa B subunit p65 was not expressed at all. These data suggest a possible underlying mechanism of signal transduction and transcriptional regulation of late-response genes after perturbations in the CNS milieu.

Distribution of AMPA receptor subunits in the hippocampal formation of temporal lobe epilepsy patients.

The immunocytochemical distribution of the AMPA-selective receptor subunits GluR1 and GluR2/3 were mapped in the human hippocampal formation obtained from surgery for medically intractable temporal lobe epilepsy. GluR2/3 immunoreactivity was detected in all principal cell types of the hippocampal formation, including hilar neurons, granule cells of the dentate gyrus, and pyramidal cells of the cornu ammonis fields and subiculum. GluR2/3 immunostaining typically filled the cell bodies and processes of neurons. A comparison of GluR2/3 immunoreactivity in a sclerotic specimen versus a non-sclerotic specimen demonstrated a profound loss of staining, specifically in the areas where neuronal dropout was occurring, including CA1, CA3 and the hilus. An analysis of GluR1 immunoreactivity in non-sclerotic specimens revealed that it was predominantly localized to cellular processes throughout the cornu ammonis fields, with a sparse staining of the dentate gyrus outer molecular layer and little to no staining of the dentate gyrus inner molecular layer. Similar to the GluR2/3-immunostained patterns, GluR1 immunoreactivity was lost in the cornu ammonis fields of sclerotic hippocampal specimens, corresponding to patterns of neuronal dropout. Our most compelling finding was a unique extensive pattern of GluR1 and Glu2/3 immunoreactivity throughout the molecular layers of the dentate gyrus of severely compromised hippocampi. The altered staining of GluR1 and GluR2/3 complements some of the patterns of axonal sprouting already described for the dentate gyrus, with a conjecture that their anatomy and distribution pattern underlies to some degree the reorganization of the sclerotic hippocampus. A combination of enhanced glutamatergic transmission and changes in neuropeptides that modulate hippocampal circuitry could greatly affect the degree of excitability in the hippocampal formation. The alterations of GluR1 and GluR2/3 immunoreactivity in the dentate gyrus add another component to the concept of reorganization in the epileptic sclerotic hippocampus.