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Biomedical subjects

B Castellano

Publications and source records attributed to B Castellano.

At least 19 recordsLinked to original sources
PubMed2006

Delayed neurodegeneration and early astrogliosis after excitotoxicity to the aged brain.

Excitotoxicity is well recognised as a mechanism underlying neuronal cell death in several brain injuries. To investigate age-dependent differences in neurodegeneration, edema formation and astrogliosis, intrastriatal N-methyl-d-aspartate injections were performed in young (3 months) and aged (22-24 months) male Wistar rats. Animals were sacrificed at different times between 12h and 14 days post-lesion (DPL) and cryostat sections were processed for Toluidine blue, Fluoro-Jade B staining, NeuN and GFAP immunohistochemistry. Our results show that both size of tissue injury and edema were reduced in the old subjects only up to 1DPL, correlating with a slower progression of neurodegeneration with peak numbers of degenerating neurons at 3DPL in the aged, contrasting with maximum neurodegeneration at 1DPL in the young. However, old animals showed an earlier onset of astroglial response, seen at 1DPL, and a larger area of astrogliosis at all time-points studied, including a greater glial scar. In conclusion, after excitotoxic striatal damage, progression of neurodegeneration is delayed in the aged but the astroglial response is earlier and exacerbated. Our results emphasize the importance of using aged animals and several survival times for the study of acute age-related brain insults.

Aging↗
PubMed2003

Nonviral gene delivery to the central nervous system based on a novel integrin-targeting multifunctional protein.

Successful introduction of therapeutic genes into the central nervous system (CNS) requires the further development of efficient transfer vehicles that avoid viral vector-dependent adverse reactions while maintaining high transfection efficiency. The multifunctional protein 249AL was recently constructed for in vitro gene delivery. Here, we explore the capability of this vector for in vivo gene delivery to the postnatal rat CNS. Significant transgene expression was observed both in the excitotoxically injured and noninjured brain after intracortical injection of the DNA-contaning-249AL vector. In the injured brain, a widespread expression occurred in the entire lesioned area and retrograde transport of the vector toward distant thalamic nuclei and transgene expression were observed. Neurons, astrocytes, microglia, and endothelial cells expressed the transgene. No recruitment of leukocytes, demyelination, interleukin-1beta expression, or increase in astrocyte/microglial activation was observed at 6 days postinjection. In conclusion, the 249AL vector shows promising properties for gene therapy intervention in the CNS, including the targeting of different cell populations.

Animals↗
PubMed2001

Expression of 27 kDa heat shock protein (Hsp27) in immature rat brain after a cortical aspiration lesion.

The 27 kDa heat shock protein (Hsp27) is a well-known member of the astroglial response to injury, playing a protective role against oxidative stress, apoptosis, and cytoskeletal destruction. Although several studies have been focused on the damaged adult brain, little is known about Hsp27 expression in the immature brain. In this work, we have examined the spatiotemporal pattern of Hsp27 expression in the normal postnatal rat brain following a cortical aspiration lesion at postnatal day 9. In the immature brain, Hsp27 is mainly observed in the internal capsule, although some scattered cells are also found in the ependyma, the corpus callosum, the septum, and hypothalamic glia limitans. In the internal capsule, Hsp27 expression is developmentally regulated, being significantly decreased from postnatal day 14. After a cortical aspiration lesion, de novo expression of Hsp27 is observed in cortical injured areas as well as in the secondary affected thalamus. In the cortex, expression of Hsp27 is first seen at day 1 postlesion (PL) surrounding the neurodegenerative area, becoming restricted to the glial scar at longer survival times. Although a pulse-like expression of Hsp27 is observed in some microglial cells at day 1 PL, most Hsp27-labeled cells are reactive astrocytes, which show GFAP overexpression and coexpress vimentin from day 3 PL. In the thalamus, astroglial Hsp27 expression is delayed, being first observed at day 5 PL. Thalamic Hsp27-labeled astrocytes do not show vimentin expression. Our observations demonstrate astroglial expression of Hsp27 in areas of tissue damage following postnatal traumatic injury, suggesting an involvement of this cytoskeleton-stabilizing protein in the remodeling processes following postnatal brain damage.

Aging↗
PubMed2001

Triflusal posttreatment inhibits glial nuclear factor-kappaB, downregulates the glial response, and is neuroprotective in an excitotoxic injury model in postnatal brain.

BACKGROUND AND PURPOSE: Nuclear factor-kappaB (NF-kappaB) and the signal transducer and activator of transcription 3 (STAT3) are important transcription factors regulating inflammatory mechanisms and the glial response to neural injury, determining lesion outcome. In this study we evaluate the ability of triflusal (2-acetoxy-4-trifluoromethylbenzoic acid), an antiplatelet agent inhibitor of NF-kappaB activation, to improve lesion outcome after excitotoxic damage to the immature brain. METHODS: Postnatal day 9 rats received an intracortical injection of the excitotoxin N-methyl-D-aspartate (NMDA) and oral administration of triflusal (30 mg/kg) either as 3 doses before NMDA injection (pretreatment) or as a single dose 8 hours after NMDA injection (posttreatment). After survival times of 10 and 24 hours, brains were processed for toluidine blue staining, tomato lectin histochemistry, and glial fibrillary acidic protein, NF-kappaB, and STAT3 immunocytochemistry. RESULTS: NMDA-lesioned animals that were not treated with triflusal showed activation of NF-kappaB in neuronal cells at first and in glial cells subsequently. Animals that received pretreatment with triflusal showed a strong downregulation of neuronal and glial NF-kappaB but a similar development of the glial response and an equivalent lesion volume compared with nontreated animals. In contrast, animals receiving triflusal posttreatment showed increased early neuronal NF-kappaB but a reduction in the subsequent glial NF-kappaB, accompanied by important downregulation of the microglial and astroglial response and a drastic reduction in the lesion size. STAT3 activation was not affected by triflusal treatment. CONCLUSIONS: Triflusal posttreatment diminishes glial NF-kappaB, downregulates the glial response, and improves the lesion outcome, suggesting a neuroprotective role of this compound against excitotoxic injury in the immature brain.

Administration, Oral↗
PubMed2000

Oral administration of the anti-inflammatory substance triflusal results in the downregulation of constitutive transcription factor NF-kappaB in the postnatal rat brain.

In this study we have evaluated the in vivo ability of triflusal (2-acetoxy-4-tri-fluoromethylbenzoic acid) to inhibit constitutive nuclear factor-kappa B (NF-kappaB) activation in the brain of postnatal rats. One week old Long-Evans black hooded rat pups received three oral administrations of triflusal (30 mg/kg) and were sacrificed at 9 days of age. After fixation, brains were cut in a cryostat and processed immunocytochemically for the demonstration of NF-kappaB. In control postnatal rats, NF-kappaB is constitutively present in some neuronal populations and in glial cells of white matter tracts. In contrast, triflusal treated rats showed a drastic downregulation of neuronal and glial NF-kappaB, both in the number of labelled cells and in the intensity of staining. The inhibition of NF-kappaB activation could be an important step in the modulation of inflammatory processes occurring after several pathological conditions.

Administration, Oral↗
PubMed2000

Neuronal, astroglial and microglial cytokine expression after an excitotoxic lesion in the immature rat brain.

Cytokines are important intercellular messengers involved in neuron-glia interactions and in the microglial-astroglial crosstalk, modulating the glial response to brain injury and the lesion outcome. In this study, excitotoxic lesions were induced by the injection of N-methyl-D-aspartate in postnatal day 9 rats, and the cytokines interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), tumour necrosis factor alpha (TNFalpha) and transforming growth factor beta 1 (TGF-beta1) analysed by ELISA and/or immunohistochemistry. Moreover, cytokine-expressing glial cells were identified by means of double labelling with glial fibrillary acidic protein or tomato lectin binding. Our results show that both neurons and glia were capable of cytokine expression following different patterns in the excitotoxically damaged area vs. the nondegenerating surrounding grey matter (SGM). Excitotoxically damaged neurons showed upregulation of IL-6 and downregulation of TNFalpha and TGF-beta1 before they degenerated. Moreover, in the SGM, an increased expression of neuronal IL-6, TNFalpha and TGF-beta1 was observed. A subpopulation of microglial cells, located in the SGM and showing IL-1beta and TNFalpha expression, were the earliest glial cells producing cytokines, at 2-10 h postinjection. Later on, cytokine-positive glial cells were found within the excitotoxically damaged area and the adjacent white matter: some reactive astrocytes expressed TNFalpha and IL-6, and microglia/macrophages showed mild IL-1beta and TGF-beta1. Finally, the expression of all cytokines was observed in the glial scar. As discussed, this pattern of cytokine production suggests their implication in the evolution of excitotoxic neuronal damage and the associated glial response.

Age Factors↗
PubMed2000

STAT3 and NFkappaB activation precedes glial reactivity in the excitotoxically injured young cortex but not in the corresponding distal thalamic nuclei.

In this study we evaluated the activation of the cytokine and growth factor responsive transcription factors signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa B (NFkappaB) after different grades of neural damage in the immature rat brain using double immunocytochemical techniques and electron microscopy. Following neocortical N-methyl-D-aspartate induced excitotoxic cell death, both these transcription factors are mainly activated in astrocytes, although microglia, endothelial cells, and neurons show transient activation at specific times and locations. Interestingly, activation of both transcription factors is only observed in cortical areas affected by severe tissue damage, neuronal degeneration, and blood-brain barrier (BBB) disruption. In contrast, the milder glial response occurring in the distal thalamus is not preceded by immunocytochemically detectable STAT3 and NFkappaB activation, although microglial response, astroglial hypertrophy, and glial fibrillary acidic protein (GFAP) overexpression do occur. In the cortex, astrocytes show STAT3 and NFkappaB activation already at 2 to 4 hours post-lesion, preceding cell hypertrophy and GFAP upregulation, and being maintained in the long-term formed glial scar. STAT3 and NFkappaB activation in microglial cells is protracted and observed at 10 to 24 hours post-lesion. The early activation of both transcription factors in astroglial cells could contribute to the changes in gene expression leading to astrogliosis and the release of signalling molecules which may contribute to the subsequent activation of these transcription factors in microglial cells.

Animals↗
PubMed1999

Primary cortical glial reaction versus secondary thalamic glial response in the excitotoxically injured young brain: microglial/macrophage response and major histocompatibility complex class I and II expression.

The excitatory amino acid analog, N-methyl-D-aspartate, was injected intracortically into nine-day-old rats. Resulting axon-sparing lesions in the developing sensorimotor cortex, which secondarily affect thalamic neurons that become deprived of cortical targets, provide an experimental model for the study of the glial response in distantly affected areas. The microglial/macrophage response was studied using tomato lectin histochemistry and major histocompatibility complex I and II immunocytochemistry. Blood-brain barrier integrity was evaluated. In the cortical lesion site, where blood-brain barrier breakdown occurs, the rapid microglial response was restricted to the degenerating area. Microglial changes were first seen at 4 h post-injection, peaking at days 3-5. Reactive microglia changed morphology, increased tomato lectin binding and expressed major histocompatibility complex I. Additionally, some cells expressed major histocompatibility complex II. In the secondarily affected thalamus, the microglial response was not as pronounced as in the cortex, was first seen at 10 h post-injection and peaked at days 3-5. Reactive microglia showed a bushy morphology, were intensely lectin positive and expressed major histocompatibility complex I. The exceptional response of the nine-day-old brain to cortical lesions makes this model an interesting tool for studying the implications of microglial major histocompatibility factor expression in still enigmatic processes such as wound healing and plasticity.

Animals↗
PubMed1999

Primary cortical glial reaction versus secondary thalamic glial response in the excitotoxically injured young brain: astroglial response and metallothionein expression.

In this study we have evaluated the primary astroglial reactivity to an injection of N-methyl-D-aspartate into the right sensorimotor cortex, as well as the secondary astroglial response in the thalamic ventrobasal complex, caused by the anterograde degeneration of descending corticothalamic fibres and/or target deprivation of the developing thalamic neurons. The astroglial response was evaluated from 4 h to 30 days post-lesion, by the immunocytochemical detection of the cytoskeletal proteins glial fibrillary acidic protein and vimentin, and the antioxidant and metal binding protein metallothionein I-II. In the lesioned cortex, hypertrophied reactive astrocytes showed increased glial fibrillary acidic protein labelling that correlated with a strong expression of vimentin and metallothionein I-II. Maximal astrocytic response was seen at one week post-lesion. The glial scar that formed later on remained positive for all astroglial markers until the last survival time examined. In contrast, in the anterogradely/retrogradely affected thalamus, the induced astroglial secondary response was not as prominent as in the cortex and was characteristically transitory, being undetectable by 14 days post-lesion. Interestingly, thalamic reactive astrocytes showed increased glial fibrillary acidic protein expression but no induction of vimentin and metallothionein I-II. In conclusion, in the young brain, the pattern of astroglial reactivity is not homogeneous and is strongly dependent on the grade of tissue damage: both in response to primary neuronal death and in response to retrograde/anterograde secondary damage, reactive astrocytes show hypertrophy and increased glial fibrillary acidic protein expression. However, astroglial vimentin and metallothionein I-II expression are only observed in areas undergoing massive neuronal death, where glial scar is formed.

Animals↗
PubMed1999

Prolongation of nerve and epidural anesthetic blockade by bupivacaine in a lipid emulsion.

UNLABELLED: We assessed the effect of a lipid emulsion of bupivacaine on prolonging peripheral nerve and epidural anesthetic blockade in the rat. The intensity and duration of motor and sensory blockade produced by a single injection of aqueous solution (BPV-as) and lipid emulsion (BPV-em) preparations of 0.5% bupivacaine were evaluated by electrophysiological methods. Both preparations induced complete, reversible motor and sensory blockade after injection. The latency time to the maximal blockade and the duration of anesthetic blockade were more prolonged for BPV-em than for BPV-as. The increase in duration of maximal blockade was 1.4 times for nerve and 1.3 times for epidural anesthesia. Histological evaluation of spinal roots and spinal cord sections did not show any abnormalities or differences between animals injected with BPV-as and those injected with BPV-em. Pharmacokinetic studies showed lower plasma peak concentration and a longer elimination half-life for BPV-em than for BPV-as. Thus, BPV-em prolongs the effects of local anesthetics, allows a similar degree of blockade, and reduces the systems toxic effects of anesthetics compared with BPV-as. IMPLICATIONS: We assessed a lipid emulsion containing bupivacaine for peripheral nerve and epidural anesthetic blockade in the rat. The emulsion allowed a complete blockade, while increasing the duration of the anesthetic effect (by 30%-40%), compared with the standard bupivacaine aqueous solution.

Anesthesia, Epidural↗
PubMed1999

Expression of growth inhibitory factor (metallothionein-III) mRNA and protein following excitotoxic immature brain injury.

The balance between trophic factors and inhibitory molecules is likely to determine the outcome of neural tissue damage. The growth inhibitory factor (GIF), a member of the metallothionein family of proteins named metallothionein-III (MT-III), has been suggested to play an important role in tissue repair after adult brain injury. Because no information is available on this factor in relation to immature brain damage, we examined the chronological changes of GIF (MT-III) mRNA and protein following excitotoxic lesions to the postnatal day 9 brain using in situ hybridization and immunocytochemical techniques. We observed a significant decrease of neuronal GIF (MT-III) mRNA and protein levels between 4 and 24 hours postinjury and an increase in glial GIF (MT-III) levels. Double immunocytochemical techniques showed GIF (MT-III) and GFAP positive astrocytes from 2-4 hours postinjury. From 3 days postinjury strongly reactive astrocytes expressed strong levels of both GIF (MT-III) mRNA and protein, which were maintained in the glial scar formed at longer times. These results show the expression of an inhibitory molecule by postnatal reactive astrocytes. Glial GIF (MT-III) expression may play an important role in the tissue reconstruction after immature brain damage.

Age Factors↗
PubMed1998

Expression of purine metabolism-related enzymes by microglial cells in the developing rat brain.

The nucleoside triphosphatase (NTPase), nucleoside diphosphatase (NDPase), 5'-nucleotidase (5'-Nase), and purine nucleoside phosphorylase (PNPase) activity has been examined in the cerebral cortex, subcortical white matter, and hippocampus from embryonic day (E)16 to postnatal day (P)18. Microglia display all four purine-related enzymatic activities, but the expression of these enzymatic activities differed depending on the distinct microglial typologies observed during brain development. We have identified three main morphologic typologies during the process of microglial differentiation: ameboid microglia (parenchymatic precursors), primitive ramified microglia (intermediate forms), and resting microglia (differentiated cells). Ameboid microglia, which were encountered from E16 to P12, displayed the four enzymatic activities. However, some ameboid microglial cells lacked 5'-Nase activity in gray matter, and some were PNPase-negative in both gray and white matter. Primitive ramified microglia were already observed in the embryonic period but mostly distributed during the first 2 postnatal weeks. These cells expressed NTPase, NDPase, 5'-Nase, and PNPase. Similar to ameboid microglia, we found primitive ramified microglia lacking the 5'-Nase and PNPase activities. Resting microglia, which were mostly distinguishable from the third postnatal week, expressed NTPase and NDPase, but they lacked or displayed very low levels of 5'-Nase activity, and only a subpopulation of resting microglia was PNPase-positive. Apart from cells of the microglial lineage, GFAP-positive astrocytes and radial glia cells were also labeled by the PNPase histochemistry. As shown by our results, the differentiation process from cell precursors into mature microglia is accompanied by changes in the expression of purine-related enzymes. We suggest that the enzymatic profile and levels of the different purine-related enzymes may depend not only on the differentiation stage but also on the nature of the cells. The use of purine-related histoenzymatic techniques as a microglial markers and the possible involvement of microglia in the control of extracellular purine levels during development are also discussed.

Animals↗
PubMed1998

Stat3 and NFkappaB glial expression after excitotoxic damage to the postnatal brain.

The nuclear factor-kappa B (NFkappaB) and the signal transducer activator of transcription 3 (STAT3), are putative transcription factors activated by growth factors and cytokines, and involved in glial gene expression changes after neuronal injury. Immunocytochemical analysis of NFkappaB and STAT3 from 2 h to 14 days after excitotoxic damage to the postnatal rat brain showed STAT3- and NFkappaB-positive glial cells at 2 h post-lesion, increasing in number to reach a maximum at day 1. Immunoreactivity then decreased but the glial scar remained positive. Glial STAT3 immunoreactivity was located in the nucleus up to 1 day post-lesion and in the nucleus, cytoplasm and cell processes from day 3. Glial NFkappaB immunoreactivity was mainly cytoplasmatic.

Acute-Phase Proteins↗
PubMed1998

Development of microglia in the postnatal rat hippocampus.

During the prenatal development of the hippocampus, microglial cell precursors progressively occur in all subfields in accordance with known ontogenetic gradients of the region (Dalmau et al., J. Comp. Neurol. 1997a;377:70-84). The present study follows the regional distribution of these microglial cell precursors and their morphological differentiation in the rat hippocampus from birth to postnatal (P) day 18. The results demonstrate that the cellular differentiation and the subregional distribution of microglia follow the specific developmental gradients of the different parts of Ammon's horn and the dentate gyrus. Microglial cell distribution in the dentate gyrus is thus delayed compared with that in Ammon's horn. The appearance of microglia in the hippocampal subregions and differentiation of cell precursors into adult microglia occur earlier at temporal levels than at septal levels. Distribution of microglial cells follows an outside-to-inside pattern from the hippocampal fissure to the main cell layers in either Ammon's horn or the dentate gyrus. Meanwhile, the resident microglial cells located in the stratum oriens and dentate hilus at birth also increase in number and gradually disperse throughout the whole tissue of the two layers with age. In Ammon's horn, microglial differentiation occurs earlier in CA3 than in CA1. In the dentate gyrus, microglia appear earlier in relation to the external limb than to the internal limb, largely following a lateral-to-medial gradient. The differentiation and appearance of microglia in the various hippocampal and dentate subregions often correspond to the developmental stage of intrinsic and extrinsic afferent nerve fiber projections. Finally, in both Ammon's horn and the dentate gyrus, cells resembling reactive microglia are also observed and, in particular, in the perforant path projections from P9 to P18, suggesting their participation not only in phagocytosis of dead cells but also in axonal elimination and/or fiber reorganization.

Acid Anhydride Hydrolases↗
PubMed1998

Understanding glial abnormalities associated with myelin deficiency in the jimpy mutant mouse.

Jimpy is a shortened life-span murine mutant showing recessive sex-linked inheritance. The genetic defect consists of a point mutation in the PLP gene and produces a severe CNS myelin deficiency that is associated with a variety of complex abnormalities affecting all glial populations. The myelin deficiency is primarily due to a failure to produce the normal amount of myelin during development. However, myelin destruction and oligodendrocyte death also account for the drastic myelin deficit observed in jimpy. The oligodendroglial cell line shows complex abnormalities in its differentiation pattern, including the degeneration of oligodendrocytes through an apoptotic mechanism. Oligodendrocytes seem to be the most likely candidate to be primarily altered in a disorder affecting myelination, but disturbances affecting astrocytes and microglia are also remarkable and may have a crucial significance in the development of the jimpy disorder. In fact, the jimpy phenotype may not be attributed to a defect in a single cell but rather to a deficiency in the normal relations between glial cells. Evidences from a variety of sources indicate that the jimpy mutant could be a model for disturbed glial development in the CNS. The accurate knowledge of the significance of PLP and its regulation during development must be of vital importance in order to understand glial abnormalities in jimpy.

Animals↗
PubMed1997

Expression of LFA-1alpha and ICAM-1 in the developing rat brain: a potential mechanism for the recruitment of microglial cell precursors.

Several studies agree that microglial cells derive from monocytes that infiltrate the central nervous system during development, but the precise mechanism by which these cells enter into the nervous tissue is still unknown. In this way, the aim of the present study was to analyze the expression of two cell adhesion molecules involved in the recruitment of blood leukocytes into tissues, the lymphocyte function-associated antigen-1alpha (LFA-1alpha) and the intercellular adhesion molecule-1 (ICAM-1) in the developing rat brain (from E16 to P18). By means of immunohistochemistry, our observations showed that LFA-1alpha and ICAM-1 were expressed in the developing rat brain with a definite distribution pattern and a characteristic time course of appearance. In the embryonic period, LFA-1alpha immunoreactivity was displayed not only by intravascular blood cells but also by intraparenchymal round cells with a horseshoe-shaped nucleus, showing the typical morphological features of monocytes. Monocyte-like cells present in the embryonic brain parenchyma often displayed mitotic profiles. LFA-1alpha immunohistochemistry also revealed the presence of some LFA-1alpha-positive cells belonging to the ameboid microglial population (mostly in the white matter from E18). In the postnatal period, LFA-1alpha immunoreactivity was displayed by some ameboid microglial cells (P0-P9) and also by some ramified microglia. LFA-1alpha immunoreactivity observed in ramified microglia was weaker when compared to LFA-1alpha stained ameboid microglia. In contrast, ICAM-1 immunolabeling during the embryonic period was mainly located in endothelial cells of parenchymal brain blood vessels (principally from day E18). Blood vessels in choroid plexus and meninges also expressed ICAM-1 during the embryonic time. In postnatal animals, ICAM-1 immunoreactivity was found in relation to endothelial cells of blood vessels, but the density of ICAM-1-positive blood vessels was lower than that during the embryonic period. The gradual regulation in the expression of LFA-1alpha by monocyte-like cells and cells of the microglial lineage, and the expression of ICAM-1 by the brain vasculature strongly suggest that the LFA-1/ICAM-1 system may be a mechanism involved in the entry of microglial cell precursors into the developing rat brain.

Aging↗
PubMed1997

Induction of metallothionein in astrocytes and microglia in the spinal cord from the myelin-deficient jimpy mouse.

Jimpy is a shortened life-span murine mutant whose genetic disorder results in severe pathological alterations in the CNS, including hypomyelination, oligodendrocyte death and strong astroglial and microglial reaction. The knowledge of metallothionein (MT) regulation in the CNS and especially of MT presence in specific glial cell types under pathological conditions is scarce. In the present study, immunocytochemical detection of MT-I + II has been performed in spinal cord sections from 10-12- and 20-22-day-old jimpy and normal animals. The identification of MT-positive glial cells was achieved through double labeling combining MT immunocytochemistry and selective markers for oligodendrocytes, astrocytes and microglia. MT was found in glial cells and was present in the spinal cord of jimpy and normal mice at both ages, but there were remarkable differences in MT expression and in the nature of MT-positive glial cells depending on the type of mouse. The number of MT-positive cells was higher in jimpy than in normal spinal cords. This was apparent in all spinal cord areas, although it was more pronounced in white than in the gray matter and at 20-22 days than at 10-12 days. The mean number of MT-positive glia in the jimpy white matter was 1.9-fold (10-12 days) and 2.4-fold (20-22 days) higher than in the normal one. Astrocytes were the only parenchymal glial cells that were positively identified as MT-producing cells in normal animals. Interestingly, MT in the jimpy spinal cord was localized not only in astrocytes but also in microglial cells. The occurrence of MT induction in relation to reactive astrocytes and microglia, and its role in neuropathological conditions is discussed.

Animals↗