Immunohistochemical profile of neurotrophins in human cranial dura mater and meningiomas

The immunohistochemical profile of neurotrophins and their receptors in the human cranial dura mater was studied by examining certain dural zones in specimens harvested from different regions (frontal, temporal, parietal and occipital). Dural specimens were obtained during neurosurgical operations performed in ten patients for surgical treatment of intracranial lesions (meningiomas, traumas, gliomas, vascular malformations). The dural fragments were taken from the area of the craniotomy at least 8 cm from the lesion as well as front the area in which the meningioma had its dural attachment. Immunohistochemical characterization and distribution of neurotrophins, with their receptors, were analyzed. The concrete role played by these neurotrophic factors in general regulation, vascular permeability, algic responsivity and release of locally active substances in the human dura mater is still controversial. Our study revealed a general structural alteration of dural tissue due to the invasivity of meningiomatous lesions, together with an improved expression of brain derived neurotrophic factor (BDNF) in highly proliferating neoplastic cells and an evident production of nerve growth factor (NGF) in inflammatory cells, suggesting that BDNF has a role in supporting the proliferation rate of neoplastic cells, while NGF is involved in the activation of a chronic inflammatory response in neoplastic areas

BDNF/TrkB Signaling as a Potential Novel Target in Pediatric Brain Tumors: Anticancer Activity of Selective TrkB Inhibition in Medulloblastoma Cells

Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Deregulation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling has been associated with increased proliferative capabilities, invasiveness, and chemoresistance in several types of cancer. However, the relevance of this pathway in MB remains unknown. Here, we show that the selective TrkB inhibitor N-[2-[[(hexahydro-2-oxo-1H-azepin-3-yl)amino]carbonyl]phenyl]-benzo[b]thiophene-2-carboxamide (ANA-12) markedly reduced the viability and survival of human cell lines representative of different MB molecular subgroups. These findings provide the first evidence supporting further investigation of TrkB inhibition as a potential novel strategy for MB treatment

Age-related changes of glutamate dehydrogenase in the rat hippocampus: an enzyme histochemical study.

Enzyme histochemical techniques associated with microphotometry were used to evaluate the reactivity of glutamate dehydrogenase (GDH) in the hippocampus of young (3 month) adult (12 month) and old (26 month) male Sprague-Dawley rats. In young rats the highest level of enzymatic reactivity was found in the stratum oriens of the CA-1-CA-4 fields followed in descending order by the molecular layer of fascia dentata, and by the layer of mossy fibers. In all the layers investigated GDH reactivity was higher in adult that in young rats. The older animals exhibited lower GDH reactivity than adult rats in almost all of the layers and higher enzymatic reactivity than in young rats in the stratum oriens of the CA-1-CA-4 fields. The hippocampus is known to be involved in the acquisition of two-way avoidance learning and is thought to utilize glutamate as one of its main neurotransmitters. These data suggest a possible relationship between hippocampal glutamatergic transmission and impairment of acquisition of avoidance learning occurring with age. Moreover, the possibility that a decreased glutamate catabolism occurring in old rats may contribute to the neuronal loss described in the hippocampus of aged rats is discussed

Nicardipine and vascular hypertrophy.

The effects of nicardipine administration on the morphology of coronary, renal, and pulmonary vascular trees were studied in spontaneously hypertensive rats (SHRs). Male 10-week-old SHRs received 1 mg/kg/day of nicardipine or vehicle orally for 12 weeks. Age-matched Wistar-Kyoto rats were used as normotensive reference animals. Blood pressure, heart weight, heart/body weight ratio, the area occupied by the medial layer, and area occupied by the vascular wall/area of lumen ratio increased significantly (p less than 0.001) in SHRs compared with normotensive Wistar-Kyoto rats. Nicardipine reduced blood pressure, as well as relative heart weight, the area occupied by vascular smooth muscle, and the area occupied by the vascular wall/area of lumen ratio. In addition, the size of laminae of smooth muscle of the pulmonary artery was reduced in nicardipine-treated SHRs; coronary artery branches were the most sensitive. The results of the study provide direct evidence that nicardipine reduces not only blood pressure but is also able to counteract the development of hypertension-dependent changes in the morphology of the cardiovascular system

A possible role of BDNF in prostate cancer detection

Many studies have demonstrated that both normal and malignant prostate cells respond to a variety of growth factors, while several significant differences were found between normal and tumoural cells. The aim of this study was to focus on the localization and distribution of the immuno-reactivity for neurotrophins (NTs) and neurotrophin receptors (NTRs) in normal, hyperplastic and prostate cancer cells, obtained from 40 subjects. We studied samples obtained from 16 prostate cancer (PC, retropubic radical prostatectomy), 20 benign prostatic hyperplasia (BPH, supra-pubic prostatectomy) and normal peripheral prostate tissue from four fresh male cadavers. Samples were examined via immunohistochemical techniques in order to detect the expression of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT3) and their own receptors TrkA, p75, TrkB and TrkC. We observed a high expression of BDNF and TrkB in PC and BPH, though no immuno-reactivity was found for p75. Low expression was reported by other NTs and NTRs in the normal peripheral prostate zone, BPH and PC. These data suggest a possible predictive role for NTs and NTRs, especially for BDNF and TrkB, in the diagnosis and/or management of prostate cancer. The absence of p75 expression confirms its supposed role in apoptotic phenomenon