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Biomedical subjects

I Mocchetti

Publications and source records attributed to I Mocchetti.

At least 37 records · Page 2Linked to original sources
PubMed1996

Increased basic fibroblast growth factor expression following contusive spinal cord injury.

Neurotrophic factors appear to be crucial for the survival and potential regeneration of injured neurons. We have previously demonstrated that contusive spinal cord injury (SCI) increases the levels of mRNA for basic fibroblast growth factor (FGF2). To determine whether FGF2 protein levels also increase, Western blot analysis was performed on extracts of spinal cord tissue after a standardized SCI and compared to laminectomy controls. In spinal cord extracts, a monoclonal antibody to FGF2 recognized various molecular forms of FGF2 (18-24 kDa) and some characteristic proteolytic fragments. Extracts of spinal cords 1 day after SCI showed a slight increase in the levels of these polypeptides. By 4 days, a significant increase (two-fold) was detected in the levels of the 18-kDa and higher molecular weight forms as well as the proteolytic fragments. Immunohistochemical analyses on spinal cord tissue sections confirmed an increased cellular (glial) FGF2 as well as interstitial immunoreactivity surrounding neurons and along blood vessels. Heparinpurified spinal cord extracts from tissue 4 days after SCI showed increased biological activity as indicated by their ability to (i) increase [3H]thymidine incorporation in cultures of Balb/c 3T3 cells and (ii) induce phosphorylation of suc-associated neurotrophic factor-induced tyrosine-phosphorylated target, a FGF2 target protein. These data suggest that SCI induces increased FGF2 expression and support the hypothesis that FGF2 may play a role in the partial recovery of function seen following SCI.

Animals↗
PubMed1996

Correlation between increased AP-1NGF binding activity and induction of nerve growth factor transcription by multiple signal transduction pathways in C6-2B glioma cells.

Transcription mechanisms regulating nerve growth factor (NGF) gene expression in the CNS are yet to be thoroughly understood. We have used C6-2B rat glioma cells to characterize the signal transduction pathways that contribute to transcriptional and posttranscriptional regulation of NGF mRNA. Because the NGF promoter contains an AP-1 consensus sequence, we have investigated whether increases in AP-1 binding activity correlate with enhanced NGF mRNA expression. Gel mobility shift assays using an oligonucleotide homologous to the AP-1 responsive element of the rat NGF gene (AP-1NGF) revealed that 12-O-tetradecanoyl phorbol-13-acetate (TPA) and, to a lesser extent, isoproterenol (ISO) and thapsigargin, a microsomal Ca(2+)-ATPase inhibitor, stimulated binding to AP-1NGF within 2 h. All of these stimuli increased NGF mRNA levels within 3 h. Cycloheximide pretreatment blocked the TPA and ISO-mediated binding to AP-1NGF suggesting that de novo synthesis of c-Fos/c-Jun may be required for the transcriptional regulation of NGF gene. Nuclear run-on assays and NGF mRNA decay studies revealed that TPA increases NGF transcription whereas ISO affects both transcription and mRNA stabilization. We propose that (i) different signal transduction mechanisms regulate the expression of the NGF gene in cells derived from the CNS, and (ii) both mRNA transcription and stability account for the cAMP-mediated increase in NGF mRNA levels.

Animals↗
PubMed1995

Induction of nerve growth factor and basic fibroblast growth factor mRNA following clenbuterol: contrasting anatomical and cellular localization.

RNase protection assay and in situ hybridization were used to analyze the temporal and cellular changes in nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) mRNA content evoked by the lipophilic beta-adrenergic receptor agonist clenbuterol in adult rat brain. Clenbuterol elicited a threefold increase in NGF mRNA expression which was limited to the cerebral cortex. This increase was maximal at 5 h, still evident by 10 h, and declined to control levels by 24 h. By 10 h NGF protein was also increased. Elevated NGF mRNA hybridization following clenbuterol was localized in the superficial cortical layers II and III in large Nissl-pale cells, suggesting that NGF mRNA induction occurs in neurons. In the same animals, clenbuterol induced a twofold increase in the levels of bFGF mRNA in cerebral cortex and hippocampus. This increase was localized primarily in glial cells as demonstrated by bFGF mRNA hybridization over all cortical regions and by labeling of the stratum lacunosum moleculare of the hippocampus. Our results suggest that enhanced noradrenergic tone regulates expression of these two trophic factors by different synaptic mechanisms and suggest that neurotransmitter(s) can coordinate trophic influences on different cell populations.

Animals↗
PubMed1995

GM1 ganglioside activates the high-affinity nerve growth factor receptor trkA.

The monosialoganglioside GM1 has been shown to possess neurotrophic activity in vitro and in vivo and is now used as an experimental treatment for a variety of neurological disorders and trauma. Little is known about the mechanism of action used by GM1. Because GM1 appears to enhance nerve growth factor (NGF) activity, we have used C6trk+ cells, a derivative of C6-2B glioma cells that express the high-affinity receptor for NGF trkA, to determine whether the neurotrophic effects of GM1 occurs through induction of trkA activity. Exposure of C6trk+ cells to NGF (10-50 ng/ml) resulted in a five- to 10-fold increase in trkA tyrosine phosphorylation within 5 min. Incubation of cells with GM1 resulted in a threefold increase in trkA phosphorylation beginning within 1 h and peaking between 3 and 6 h. Optimal responses to GM1 were obtained using 80-100 microM concentrations. Moreover, tyrosine phosphorylation of known trkA target proteins, such as extracellular signal-regulated kinases, and suc-associated neurotrophic factor-induced tyrosine-phosphorylated target, were activated upon stimulation of C6trk+ cells with GM1. In addition, GM1 potentiated the NGF-mediated activation of tyrosine phosphorylation of trkA. GM1 failed to induce phosphorylation of trkA and target proteins in mock transfected cells. Thus, our data demonstrate that GM1 mimics some of the effects of NGF and suggest that the neurotrophic properties of GM1 may be attributed to its activation of trkA signal transduction.

Dose-Response Relationship, Drug↗
PubMed1995

Neurotrophic factors in central nervous system trauma.

Although regeneration of injured neurons does not occur after trauma in the central nervous system (CNS), there is often significant recovery of functional capacity with time. Little is currently known about the molecular basis for such recovery, but the increased trophic activity in injured CNS tissue and the known properties of neurotrophic factors in neuronal growth and maintenance suggest that these polypeptides are probably involved in recovery of function. Members of the neurotrophin family, including nerve growth factor (NGF), brain-derived neurotrophic factors (BDNF), and neurotrophin 3 (NT-3), are capable of supporting survival of injured CNS neurons both in vitro and in vivo. They also stimulate neurite outgrowth, needed for reorganization of the injured CNS, and the expression of key enzymes for neurotransmitter synthesis that may need to be upregulated to compensate for reduced innervation. The effects of the neurotrophins are mediated through specific high affinity trk receptors (trk A, B, C) as well as a common low affinity receptor designated p75NGFR. Another class of neurotrophic polypeptides also provides candidate recovery-promoting molecules, the heparin-binding growth factors' acidic and basic fibroblast growth factor (aFGF, bFGF). FGFs not only sustain survival of injured neurons but also stimulate revascularization and certain glial responses to injury. Both the neurotrophins and the FGFs, as well as their respective receptors, have been shown to be upregulated after experimental CNS injury. Further, administration of neurotrophins or FGF has been shown to reduce the effects of experimental injury induced by axotomy, excitotoxins, and certain other neurotoxins. The cellular basis for the potential therapeutic use of neurotrophic molecules is discussed as well as new strategies to increase neurotrophic activity after CNS trauma based on the recently obtained information on pharmacological and molecular control of the expression of these genes.

Animals↗
PubMed1995

Expression of c-kit receptor and its autophosphorylation in immature rat type A spermatogonia.

The objective of this study was to examine the expression and activation of the c-kit receptor, a specific receptor for kit ligand (stem cell factor, steel factor), in rat type A spermatogonia. Testes were obtained from 9-day-old rats, decapsulated, and then subjected to sequential enzymatic digestion. The mixture of testicular cell types was then separated by sedimentation velocity at unit gravity. The isolated type A spermatogonia were characterized by light and electron microscopy. They exhibited spherical nuclei containing several nucleoli and associated chromatin clumps and organelles generally in a perinuclear location similar to that found in the in vivo 9-day-old testis. The synthesis of the c-kit receptor by the spermatogonia was established by hybridization of total RNA with a specific cDNA for mouse c-kit receptor. Two mRNA transcripts migrating at 4.8 kb and 12 kb were observed. Localization of the c-kit receptor in the isolated cells was determined by immunocytochemistry using an antibody to c-kit protein. Specific staining for c-kit receptor was observed in the cytoplasm of the isolated type A spermatogonia. Furthermore, the presence of the c-kit receptor protein in the spermatogonia was confirmed by Western blot analysis using the same antibody. The antibody recognized the c-kit receptor at approximately 160 kDa. In an attempt to determine whether this receptor has a functional significance, we examined the effect of kit ligand on the phosphorylation of the c-kit receptor. The c-kit receptor appeared to be constitutively autophosphorylated on tyrosine at low basal levels, and upon stimulation with kit ligand, the amount of phosphorylated protein increased significantly. These observations indicate that kit ligand induces autophosphorylation of the c-kit receptor, which may lead to the activation of other cellular target proteins responsible for spermatogonial proliferation and/or differentiation.

Animals↗
PubMed1994

Induction of nerve growth factor responsiveness in C6-2B glioma cells by expression of trkA proto-oncogene.

Cells that lack the high affinity receptor component (trkA) for nerve growth factor (NGF) are unresponsive to NGF. We investigated whether C6-2B cells, a rat glioma derived cell line, express trkA and, as a consequence, are responsive to NGF. In these cells, NGF (100 ng/ml) failed to induce the mRNA encoding for c-fos protooncogene and the low affinity NGF receptor p75NGFR, two NGF-responsive genes. In contrast, both mRNAs were induced in PC12 cells by NGF. Using a RNase protection assay with a cRNA probe for rat trkA, the expected trkA RNA protected fragment was detected in PC12 but not in C6-2B glioma cells, indicating that C6-2B cells either do not express the gene or express it only in low amounts. Cross-linking of 125I-labeled NGF to PC12 cells identified two major bands with an apparent molecular weight of 158 kDa and 100 kDa corresponding to trkA and p75NGFR, respectively. In contrast, only the 100 kDa band could be detected in C6-2B cells by cross-linking analysis. In C6-2B cells stably transfected with the rat trkA cDNA, NGF increased c-fos mRNA, induced tyrosine phosphorylation of gp140trk, and SNT (suc-associated neurotrophic factor-induced tyrosine-phosphorylated target), and caused morphological changes within 72 h. All of these effects of NGF were blocked by the protein kinase inhibitor K-252a suggesting that NGF signal transduction was restored by trkA expression. Most important, in C6trk+ cells, NGF was a weaker (2-fold) inducer of [3H]thymidine incorporation when compared to bFGF (5-fold), suggesting that expression of trkA fails to confer to NGF a strong mitogenic effect. Our findings indicate that C6-2B glioma cells do not possess high affinity NGF receptor and thus are unresponsive to NGF and that expression of trkA in neuroectoderm derived cells elicits some of the NGF responses characteristic of neuronal cells.

Animals↗
PubMed1994

Regional and temporal pattern of expression of nerve growth factor and basic fibroblast growth factor mRNA in rat brain following electroconvulsive shock.

We have previously reported that focally evoked limbic motor seizures rapidly increase levels of mRNA encoding nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) in specific limbic system areas of the adult rat brain. The present studies examined the effect of both minimal and maximal electroconvulsive shock, applied via corneal electrodes, on NGF and bFGF mRNA levels in several limbic (entorhinal cortex, hippocampus, olfactory bulb) and extralimbic (striatum and cerebellum) brain regions. By 5 h following limbic motor seizures induced by low-intensity (minimal) electroshock (LES) (0.2 s, 50-70 mA; three times over a 1-h period), bFGF mRNA was significantly increased in entorhinal cortex and hippocampus, but not in the other regions examined. In contrast, tonic extensor seizures evoked by maximal electroshock (MES) (0.2 s, 150 mA; three times over a 1-h period) were associated with a significant increase in bFGF mRNA in all limbic and extralimbic regions examined. In the same animals, increases in NGF mRNA were limited to entorhinal cortex and hippocampus. Adrenal steroids were not required for the seizure-induced increase in NGF or bFGF mRNAs, based on the finding that adrenalectomized rats exhibited electroshock-induced increases in both NGF and bFGF mRNAs equivalent to the increase observed in sham-operated rats. It is suggested that the increase in mRNA levels for the neurotrophic factors occurs selectively in those regions which are especially activated by the specific seizure model, and represents an adaptive response to repeated noninjurious neuronal stimulation.

Adrenalectomy↗
PubMed1994

Increased basic fibroblast growth factor mRNA following contusive spinal cord injury.

Neurotrophic factors appear to be crucial for the survival and potential regeneration of injured neurons. Injury of the peripheral nervous system results in the induction of a number of neurotrophic molecules. Less is known about the response of central nervous tissue to injury. We have examined changes in levels of mRNA for three trophic factors, basic and acidic fibroblast growth factor (bFGF, aFGF), and nerve growth factor (NGF), after a standardized incomplete thoracic contusive spinal cord injury (SCI). RNase protection assays showed a rapid increase (3-fold) in the content of bFGF mRNA by 6 hours after SCI in tissue that included the injury site. No effect of injury was seen in segments of cervical or lumbar cord. bFGF mRNA at the injury site remained significantly increased at 1 and 7 days after SCI. Further, at 7 days, the increase was anatomically restricted to the rostral portion of the injury site suggesting the involvement of specific pathways in the maintenance of high levels of bFGF mRNA. No change in the levels of aFGF mRNA was seen after SCI. Similarly, no difference in the expression of the mRNA for NGF or its high affinity receptor (trkA), were observed at 6 h, 1 or 7 days following SCI. Our observation of a specific effect of SCI on bFGF mRNA expression supports a speculative hypothesis that bFGF may play a role in the partial recovery of function seen following incomplete contusive spinal cord injury.

Animals↗
PubMed1993

Adrenal steroids mediate the increase of hippocampal nerve growth factor biosynthesis following bicuculline convulsions.

Northern blot analysis of nerve growth factor (NGF) messenger ribonucleic acid (mRNA), together with a two-site enzyme immunoassay for NGF protein, showed that a convulsive dose of bicuculline (0.4 mg/kg, IV) induced a rapid (within 1 hour) three-fold increase in hippocampal NGF mRNA. This increase was followed by a significant increase in NGF protein 5 hours later. No changes were detected in the cerebral cortex. The increase of rat hippocampal NGF mRNA and protein content was associated with an increase in plasma corticosterone content. Both responses were completely prevented by a pretreatment with diazepam (5 mg/kg, IP), which suggested that adrenal steroids might be a stimulus underlying the rapid increase in NGF biosynthesis following bicuculline convulsions. Therefore, we tested to determine whether a convulsive dose of bicuculline could increase NGF mRNA in adrenalectomized and sham-operated rats. Bicuculline increases hippocampal NGF mRNA in sham-operated rats, but not in adrenalectomized rats despite the presence of convulsions in both experimental groups. Moreover, in adrenalectomized rats, dexamethasone (0.5 mg/kg, SC) could partly restore the increase in hippocampal NGF mRNA content induced by bicuculline convulsions; thus, adrenal steroids might have an essential role in the induction of hippocampal NGF biosynthesis elicited by bicuculline convulsions.

Adrenal Cortex Hormones↗
PubMed1993

Regulation of basic fibroblast growth factor and nerve growth factor mRNA by beta-adrenergic receptor activation and adrenal steroids in rat central nervous system.

Basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) are two neurotrophic factors that play a role in neuronal maintenance and repair. The identification and characterization of mechanisms regulating neurotrophic factor availability in the central nervous system are vital to the development of therapeutic tools for prevention of neuronal degeneration. The lipophilic beta-adrenergic receptor (BAR) agonist clenbuterol was used to assess whether activation of central BAR changes the levels of NGF and bFGF mRNA. Within 5 hr, clenbuterol (10 mg/kg, intraperitoneally) elicited a 2-3-fold increase in bFGF and NGF mRNA content in rat cerebral cortex. The induction of bFGF and NGF mRNA expression showed anatomical specificity. Among the various brain areas examined, bFGF mRNA levels were increased in the cerebral cortex, hippocampus, and cerebellum, whereas induction of NGF mRNA was observed only in the cerebral cortex. Isoproterenol, a BAR agonist that does not cross the blood-brain barrier, also elicited a 2-3-fold increase in bFGF and NGF mRNA in the cerebral cortex. Propranolol (5 mg/kg, intraperitoneally), a lipophilic BAR antagonist, blocked the induction of NGF and bFGF mRNA mediated by either isoproterenol or clenbuterol, whereas nadolol (5 mg/kg, intraperitoneally), a BAR antagonist that does not cross the blood-brain barrier, blocked only the effect of isoproterenol. Therefore, activation of both central and peripheral BAR play a role in the regulation of bFGF and NGF mRNA expression. Moreover, in adrenalectomized rats, isoproterenol failed to increase bFGF and NGF mRNA, whereas clenbuterol elicited a 2-fold increase in bFGF mRNA in the cortex and hippocampus. Our data suggest that both adrenal steroids and noradrenaline might regulate the availability of selective neurotrophic factors in the adult central nervous system.

Adrenal Cortex Hormones↗
PubMed1993

Characterization of a decrease in muscarinic m2 mRNA in cerebellar granule cells by carbachol.

Studies involving carbachol (100 microM) treatment of cerebellar granule cells for 1, 3, 6, 9, 12 and 24 hr show a decrease in the mRNA encoding for the muscarinic m2 receptor. The response was transient, decreasing m2 mRNA by 25 to 50% in 6 and 9 hr, respectively. The data presented in this work were quantified by ribonuclease protection assay, using a [32P]-cRNA probe corresponding to nucleotide +1138 to 1650 of the rat m2 muscarinic receptor. Because cerebellar granule cells express muscarinic m2 and m3 receptors, we tested whether the carbachol-mediated decrease in m2 mRNA resulted from a homologous or heterologous activation of muscarinic receptors. At a 1 microM concentration, methoctramine specifically blocked the muscarinic m2 receptor and reversed carbachol's action. These data suggested that carbachol acts via a possible homologous activation of muscarinic m2 receptors. The half-life of the receptor mRNA measured in the presence of actinomycin D with and without carbachol were similar. Because carbachol treatments decrease the steady-state levels of m2 mRNA without changing the half-life of the message, we suggest that a carbachol treatment induces a decrease in the transcription of the gene for the muscarinic m2 receptor.

Animals↗
PubMed1992

Dopaminergic regulation of cholecystokinin mRNA content in rat striatum.

The nigrostriatal dopaminergic activity was pharmacologically changed to assess whether dopamine (DA) regulates cholecystokinin (CCK) mRNA steady state in rat striatum. Cocaine and benztropine, two dopaminergic agonists known to induce DA release and to block its re-uptake, produced a time dependent increase in CCK mRNA content in rat striatum. A significant increase in striatal CCK mRNA was observed 8 h after a single injection of cocaine (15 mg/kg, i.p.) or benztropine (15 mg/kg, i.p.) whereas a two-fold increase was observed after a daily treatment for one week with these two dopaminergic agonists. Cocaine and benztropine failed to change CCK mRNA content in the cerebral cortex. Haloperidol, a dopaminergic receptor blocker, injected at 1 mg/kg, i.p., daily for 7 days, decreased CCK mRNA content in striatum but not in the cerebral cortex. Moreover, haloperidol blocked the effect of cocaine and benztropine, suggesting that the stimulation of striatal dopaminergic receptors is necessary for the induction of CCK biosynthesis. The neurotoxin 6-hydroxydopamine injected into the medial forebrain bundle, elicited a 50% decrease in striatal CCK mRNA, supporting the hypothesis that DA tonically regulates CCK biosynthesis in postsynaptic neurons. To characterize the dopaminergic receptor subtype involved in this regulation, BHT 920, a specific D2 receptor agonist and SKF 38393, a specific D1 receptor agonist were used. While one week treatment with BHT 920 (1 mg/kg, i.p.) increases striatal CCK mRNA content, SKF 38393 (3 mg/kg, i.p.) failed to change this parameter. These data suggest that the increase of striatal CCK mRNA is mediated by the activation of the D2 receptor subtype.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Basic fibroblast growth factor mRNA increases in specific brain regions following convulsive seizures.

Basic fibroblast growth factor (bFGF) is a trophic factor synthesized in the central nervous system (CNS), where it is believed to play a role in neuronal maintenance and repair. Little is known about the regulation of this growth factor in the CNS. To determine whether the expression of the bFGF gene in the brain of adult animals changes in response to alterations of neuronal activity, we examined bFGF mRNA levels in several brain regions of rats experiencing focally-evoked convulsive seizures. Seizures were induced by microinjecting bicuculline unilaterally into an epileptogenic site within the deep prepiriform cortex, area tempestas (AT). By 5 h after initiation of brief limbic motor seizures from AT, there was a four fold increase in the levels of bFGF mRNA in the entorhinal cortex, hippocampus and olfactory bulb, but not in the caudate-putamen. The maximal expression of bFGF mRNA was reached by 10 h after seizure onset. In the same animals, the mRNA encoding nerve growth factor (NGF) was increased in entorhinal cortex and hippocampus, but not in the olfactory bulb. Our results demonstrate that neuronal activity can influence bFGF expression in an anatomically selective fashion and that acute changes in bFGF can occur in the uninjured mature brain. The increase in bFGF expression in response to excessive activation of specific neuronal circuitry may represent an adaptive response to protect against potential injury in those circuits.

Animals↗
PubMed1992

Regulation of cholecystokinin mRNA content in rat striatum: a glutamatergic hypothesis.

Changes in the cholecystokinin (CCK) mRNA content in rat striatum after the administration of specific glutamate and dopamine (DA) receptor agonists and antagonists were investigated. MK-801 (1 mg/kg i.p.), a selective noncompetitive N-methyl-D-aspartate (NMDA)-sensitive glutamatergic receptor antagonist, but not 6-cyano-7-nitroquinoxaline-2,3-dione (1.1-9.2 micrograms i.c.v.), a competitive non-NMDA glutamatergic receptor antagonist, produced a time- and dose-dependent decrease in striatal CCK mRNA. The maximum inhibition (50%) was observed after a daily treatment for 1 week with MK-801 (1 mg/kg). The activation of NMDA receptors by a single injection of NMDA (1.4 micrograms i.c.v.) elicited an 80% increase in CCK mRNA in rat striatum 8 hr after the injection. These data suggest that glutamate exerts a tonic regulation on striatal CCK mRNA, mainly through NMDA-sensitive glutamatergic receptors. B-HT 920, a DA D2 receptor agonist and benztropine, a DA uptake blocker, increased striatal CCK mRNA. This increase was partially blocked by the concomitant administration of MK-801. Moreover, the DA receptor antagonist haloperidol, at a dose that per se failed to change CCK mRNA (0.3 mg/kg i.p.), partially blocked the increase in CCK mRNA elicited by NMDA. Similarly, the NMDA effect was attenuated in rats with a 6-hydroxydopamine-induced nigrostriatal lesion. Our findings suggest that in rat striatum a complex DA-glutamate interaction tonically regulates CCK expression via D2 and/or NMDA receptor activation.

Animals↗
PubMed1991

Developmental expression of the basic fibroblast growth factor gene in rat brain.

Basic fibroblast growth factor (bFGF) is a trophic factor for a variety of neuronal/glial cell populations. The RNase protection assay, with a cRNA complementary to the coding region of bFGF mRNA, was used to investigate the brain distribution and developmental regulation of bFGF mRNA expression. In adult rats bFGF mRNA is distributed throughout the brain, the highest levels being observed in cerebral cortex, hippocampus and spinal cord. The levels of bFGF mRNA in all the brain structures are low in newborn rats, increase thereafter to reach a peak of expression around postnatal day 21. bFGF mRNA levels are significantly different between various brain structures during the first and second postnatal week. Adult and aged rats (Fisher 344) express the same levels of bFGF mRNA in the various brain regions. The onset of bFGF mRNA expression suggests that this growth factor is important for the maturation as well as for the maintenance of different cell populations of the central nervous system.

Aging↗
PubMed1991

Localization of nerve growth factor receptor mRNA in contused rat spinal cord by in situ hybridization.

Northern blot analysis using a probe for the low-affinity nerve growth factor receptor (NGFR) revealed that a mild contusive injury induces the expression of NGFR mRNA in rat spinal cord with a maximal expression at 7 days post-injury. We have now localized this induction using in situ hybridization and found the highest concentration of NGFR mRNA at the lesion epicenter. The location and pattern of autoradiographic grains were compared with that of various cell types at the injury site as determined by immunocytochemical studies. The results suggest that cells associated with blood vessels at the epicenter are induced to express NGFR mRNA at 7 days post-injury.

Animals↗