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F Gómez-Pinilla

Publications and source records attributed to F Gómez-Pinilla.

30 records · Page 2Linked to original sources
PubMed1992

Transient lesion-induced increase of basic fibroblast growth factor and its receptor in layer VIb (subplate cells) of the adult rat cerebral cortex.

Basic fibroblast growth factor is a potent trophic factor with a wide spectrum of activity at various stages of neuronal development. In our studies on the effects of select lesions on the expression of growth factors, we observed that neurons of layer VIb of the rat cerebral cortex developed immunoreactivity for basic fibroblast growth factor and its receptor following injury. Recent evidence indicates that layer VIb of the rat cerebral cortex contains the subplate cell population, a group of neurons shown to participate in the development of the cerebral cortex. In this article, we examined the nature and time-course of the response to injury of the expression of basic fibroblast growth factor and its receptor in these cells. We used an anti-basic fibroblast growth factor monoclonal antibody that recognizes the active form of basic fibroblast growth factor, and a polyclonal antibody that recognizes the extracellular domain of the basic fibroblast growth factor receptor. The induction of basic fibroblast growth factor and its receptor in layer VIb cells occurred after entorhinal cortex lesion, fimbria-formix transection or aspiration of small segment of the frontoparietal cortex. The lesion-induced effect was transient, appearing by postlesion day 2 and having disappeared by postlesion day 7. These findings suggest that endogenous basic fibroblast growth factor may have a neuroprotective role on layer VIb neurons after trauma and/or may participate in cortical plasticity during adulthood.

Animals↗
PubMed1992

Basic FGF in adult rat brain: cellular distribution and response to entorhinal lesion and fimbria-fornix transection.

Basic fibroblast growth factor (bFGF) is a potent trophic factor for neurons and astrocytes and recently has been implicated in the pathology of Alzheimer's disease. In order to better understand the role of bFGF in normal brain function and during pathology, we have analyzed its anatomical distribution and its response to injury in the CNS. Double-staining immunohistochemistry showed that bFGF immunoreactivity was localized in astrocytes, in select neuronal populations, and occasionally in microglial cells throughout the normal rat brain. Neuronal populations that showed bFGF immunoreactivity included septohippocampal nucleus, cingulate cortex, subfield CA2 of the hippocampus, cerebellar Purkinje cells, cerebellar deep nuclei, facial nerve nucleus, and the motor and spinal subdivisions of the trigeminal nucleus and facial nerve nucleus. The pattern of bFGF immunoreactivity in the hippocampus was examined following entorhinal cortex lesion, or fimbria-fornix transection. After entorhinal cortex lesion, bFGF immunoreactivity increased in the outer molecular layer of the dentate gyrus ipsilateral to the lesion. The lesion effect on bFGF immunoreactivity was expressed as an increase in the number of bFGF astrocytes, as an increase in the intensity of bFGF immunoreactivity within astrocytes, and as an increase of bFGF immunoreactivity in the surrounding extracellular matrix, relative to the contralateral side. The time course and pattern of reorganization paralleled the sprouting of septal cholinergic terminals in response to the same type of lesion, suggesting that bFGF may play an important role in lesion-induced plasticity. After transection of the fimbria-fornix, chronic infusion of bFGF appeared to preserve NGF receptors on neurons within the medial septal complex and, as previously reported, prevent the death of medial septal neurons. Therefore, it appears that bFGF infusion, which has been shown to increase the synthesis of NGF by astrocytes (Yoshida and Gage, 1991), also helps enable neurons to respond to NGF. This suggests that after injury bFGF may participate in a cascade of neurotrophic events, directly and indirectly facilitating neuronal repair and/or promoting neuronal survival.

Animals↗
PubMed1989

NGF receptor increase in the olfactory bulb of the rat after early odor deprivation.

In the olfactory bulb of normal rats, nerve growth factor (NGF) receptor (NGFR) immunoreactivity was largely confined to the glomerular layer. Unilateral closure of the nostril at postnatal day 2 (P2) increased NGFR immunoreactivity in the sealed bulb at both 19 and 60 days after the operation. The increase in NGFR density, measured by autoradiographic immunohistochemistry, was most dramatic 60 days postocclusion. These findings suggest that a compensatory increase in NGFRs may play a role in the maintenance of bulbar function after the early loss of sensory stimulation.

Animals↗
PubMed1989

NGF receptor immunoreactivity in aged rat brain.

The cellular distribution of nerve growth factor (NGF) receptor (NGFR) immunoreactivity in 3 cholinergic nuclei (medial septal nucleus, nucleus of the diagonal band and nucleus basalis magnocellularis) of the aged rat brain was compared to that of young-adult animals. In young-adult rats, NGFR immunoreactivity was strong in the neuronal body and in the whole dendritic tree. In aged animals, NGFR immunoreactivity was weak in both cell body and dendrites and was practically absent in the dendrite's distal portion. The loss of dendritic NGFR may play a critical role in the decline of neuronal function in the aging brain.

Aging↗
PubMed1989

Neuroprotective effect of MK-801 and U-50488H after contusive spinal cord injury.

One hour before a contusive spinal cord injury either compound MK-801 or compound U-50488H was injected intraperitoneally, and a 14-day-delivery osmotic minipump containing the same drug was placed subcutaneously at the time of surgery. The motor and sensory behavior of the animals was measured over the following 30 days. Both MK-801 and U-50488H treatments had a statistically significant neuroprotective effect. The number of neurons per unit area outside the lesion epicenter was significantly (P less than 0.01) greater in the drug-treated animals (MK-801, 298.9 +/- 74.8 neurons/mm2; U-50488H, 242.7 +/- 16.5 neurons/mm2) than in untreated controls (73.3 +/- 9.3 neurons/mm2). Recovery of sensory and motor behavior was limited but significant differences were observed when drug-treated rats were compared with untreated controls. The effects of the two drugs were not additive for any of the variables studied.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1989

Motor cortex projections to the thalamus. An autoradiographic study in the cat.

Adult cats received tritiated proline-leucine injections into the pericruciate cortex (areas 4 gamma and 3a) unilaterally and the projections to the thalamus were analyzed. Ipsilateral projections were found in the following nuclei, from rostral to caudal: ventral anterior, reticular, ventral lateral, central medial, paracentral, central lateral, ventral medial, mediodorsal, ventral posterolateral, ventral posteroinferior, centre median, parafascicular and posterior complex. In the contralateral hemithalamus sparse projections were found within the paracentral, central lateral and ventral medial nuclei.

Animals↗
PubMed1988

Epidermal growth factor receptor immunoreactivity in rat brain astrocytes. Response to injury.

Brain astroglia in normal adult rats stained weakly or not at all with an antibody to epidermal growth factor receptor (EGFR). A dramatic change took place after injury. The astrocytes adjacent to an entorhinal ablation and in deafferented areas of the hippocampus showed prominent EGFR immunoreactivity. Cells that were EFGR-immunoreactive also stained intensely with an antibody to glial fibrillary acidic protein (GFAP). The localization and the time course of appearance of EGFR/GFAP immunoreactivity suggests that EGFR may be involved in the conversion of a normal into a reactive astrocyte.

Aging↗
PubMed1988

Epidermal growth factor receptor immunoreactivity in rat brain. Development and cellular localization.

In rat brain, distinct epidermal growth factor-receptor immunoreactivity (EGFR-IR) first appeared in astroglia at about day 16 postnatal, reached maximum intensity at 19 days and then became much weaker as the animals reached adulthood. EGFR-IR was also observed in cerebellar Purkinje cells as early as 11 days postnatal and was maintained into adulthood. In adult and aged animals the most prominent EGF receptor immunostaining occurred in cerebral cortex neurons (layers IV and V) that had the morphology of basket cells. Immunoreactive neurons were abundant in the cingulate, frontal, frontoparietal and striate cortices. In the frontoparietal cortex, EGFR positive neurons were most numerous in the motor area, diminishing laterally towards the somatosensory area. The localization and time of appearance of EGFR-IR did not appear consistent with a direct mitogenic role of the EGF domain in astroglia proliferation during development. However, the EGFR may be involved in neuronal survival and/or neuron-glia signalling.

Aging↗
PubMed1987

Novel crossed corticothalamic projections after neonatal cerebral hemispherectomy. A quantitative autoradiography study in cats.

This is a quantitative study of remodeling of the corticothalamic projections in cats with a left cerebral hemispherectomy performed neonatally or in adulthood. Kittens were lesioned at a mean postnatal age of 10 days and compared, as adults, to adult-lesioned cats of prolonged survival time. All cats received injections of [3H]leucine-proline in the right pericruciate cortex and were sacrificed 5 days later. Injection site and terminal field areas were reconstructed from autoradiography-processed tissue. For the 3 animal groups the label filled a similar extent of cortical areas 4 gamma and 3a. Computerized procedures were used to count labeled particles from multiple bilateral sites of ventral thalamic nuclei (VTN), intralaminar nuclei and midline/paramedial regions at 2 thalamic coronal planes. In control cats the only labeling in the hemithalamus contralateral to the injection was in the intralaminar nuclei and medial-most region of VTN but the counts were low. In contrast, the contralateral hemithalamus of neonatal-lesioned cats showed: a significant increase in terminal field density relative to control cats throughout the VTN, at both coronal planes, and with a distribution of labeling different to the intact side (suggesting heterotypic growth); an increase in counts of labeled particles in intralaminar nuclei which was significant for one sampling site; and an increase in counts for midline/paramedial regions which was significant for all sites at the caudal plane. Adult hemispherectomized cats were similar to intacts except for a tendency to increased VTN counts. These novel terminals were interpreted as collateral sprouting of corticofugal fibers from the intact motor cortex which crossed the midline to reinnervate the decorticate hemithalamus. Findings are discussed in the context of our reported behavioral and anatomical results.

Age Factors↗
PubMed1986

Reorganization of pericruciate cortical projections to the spinal cord and dorsal column nuclei after neonatal or adult cerebral hemispherectomy in cats.

This is a quantitative study of changes in distribution and density of terminals of the corticospinal tract in the cervical spinal cord and dorsal column nuclei (DCN) in cats with left cerebral hemispherectomy performed neonatally or in adulthood. Kittens received hemispherectomy at a mean of 12.1 postnatal days and were compared, as adults, to adult-lesioned cats of similar survival time. All animals, including controls, received injections of [3H]leucine-proline and were sacrificed 5 days later. Injection sites and terminal fields were reconstructed from autoradiography-processed tissue. The label filled comparable extents of areas 4 gamma and 3a of the right cerebral cortex. Coronal sections from upper and lower cervical cord levels, and from the brainstem (cuneate and gracile nuclei) were studied. Computer-image processing procedures were used to count labeled particles from multiple sites of the dorsal horn and DCN, bilaterally. In the spinal cord of intact and adult-hemispherectomized cats, most terminals were found in lamina VI, and adjacent laminae V and VII contralateral to the injection side. The major finding was that neonatal-lesioned cats showed a significant increase in axon terminals in areas ipsilateral to the injection. The topography of distribution of the novel terminals was similar to that in the contralateral side and the originating fibers appeared to have crossed the midline from that side. A similar reorganization occurred in the gracile nucleus where, in intact and adult-lesioned cats, the cortical terminals also predominated in the side contralateral to the injection. In contrast, neonatal-lesioned animals showed a significant increase in terminal density ipsilateral to the cortical injection. These findings are discussed as an alternative mechanism for postlesion remodeling of the corticospinal tract in animals with the pyramidal crossing completed at the time of birth.

Age Factors↗
PubMedDate not supplied

Induction of basic fibroblast growth factor in Alzheimer's disease pathology.

Alzheimer's disease (AD) and its hallmark, plaques, may be due to an imbalance of trophic support. It has been suggested that plaque biogenesis may involve a growth factor which induces sprouting of neurites to form plaques. Thus, we studied the distribution of basic fibroblast growth factor (bFGF), in the hippocampus from AD brain and in rodent brain after entorhinal ablation. Both cases have a partial deafferentation of the hippocampus. The strongest bFGF immunoreactivity in AD was shown in plaques of the dentate gyrus. Rodent brains showed a lesion-induced increase of bFGF in the dentate gyrus, primarily localized to astrocytes. Our results indicate that bFGF may serve an important biological function in plaques and possibly attract neurites.

Alzheimer Disease↗