Biomedical subjects

P Levitt

Publications and source records attributed to P Levitt.

At least 73 records · Page 4Linked to original sources

PubMed1995

The limbic system-associated membrane protein is an Ig superfamily member that mediates selective neuronal growth and axon targeting.

The formation of brain circuits requires molecular recognition between functionally related neurons. We report the cloning of a molecule that participates in these interactions. The limbic system-associated membrane protein (LAMP) is an immunoglobulin (Ig) superfamily member with 3 Ig domains and a glycosyl-phosphatidylinositol anchor. In the developing forebrain, lamp is expressed mostly by neurons comprising limbic-associated cortical and subcortical regions that function in cognition, emotion, memory, and learning. The unique distribution of LAMP reflects its functional specificity. LAMP-transfected cells selectively facilitate neurite outgrowth of primary limbic neurons. Most striking, administration of anti-LAMP in vivo results in abnormal growth of the mossy fiber projection from developing granule neurons in the dentate gyrus of the hippocampal formation, suggesting that LAMP is essential for proper targeting of this pathway. Rather than being a general guidance cue, LAMP likely serves as a recognition molecule for the formation of limbic connections.

Amino Acid Sequence↗

PubMed1995

Regulation of regional differences in the differentiation of cerebral cortical neurons by EGF family-matrix interactions.

Both lineage-based and epigenetic regulation have been postulated as mechanisms to control the formation of discrete areas in the cerebral cortex, but specific genes or signaling pathways that may be involved have yet to be defined. In this paper, we examine whether progenitors, isolated from the cerebral wall prior to neurogenesis, can respond to exogenous cues by adopting a region-specific phenotype. The expression of the limbic system-associated membrane protein (LAMP), a neuron-specific marker of limbic cortical areas, was monitored in cultured neurons arising from precursors harvested from presumptive perirhinal (limbic) and sensorimotor (nonlimbic) zones at embryonic day 12 in the rat. Neuronal phenotype in all cultures was identified by expression of microtubule-associated protein-2 (MAP2). On a substrate of poly-lysine, over 80% of the precursors from the limbic area that differentiate into neurons express a LAMP+ phenotype. Approximately 20% of the neurons generated from precursors of the sensorimotor region become LAMP+. However, modification of the microenvironment had a significant effect on the differentiation of the sensorimotor precursors. When the nonlimbic precursors are grown on Matrigel, there is a 2-fold increase in the number of MAP2+/LAMP+ double-labeled neurons. Dissection of the Matrigel components reveals that in combination with growth factor-deficient Matrigel or collagen type IV, epidermal growth factor and transforming growth factor-alpha increase LAMP expression in the sensorimotor population. Delaying the addition of growth factor until after most cell division had ceased failed to increase the number of LAMP+ neurons. Another growth factor in Matrigel, platelet-derived growth factor, does not produce the same effect. Our results indicate that local signals can regulate the differentiation of cortical progenitors, providing a potential mechanism for establishing an early commitment to specific regional phenotypes in the developing cerebral wall that relate to future functional domains in the cortex.

Animals↗

PubMed1995

The limbic system-associated membrane protein (LAMP) selectively mediates interactions with specific central neuron populations.

The limbic system-associated membrane protein (LAMP) is a 64-68 x 10(3) M(r) glycoprotein that is expressed by subsets of neurons that are functionally interconnected. LAMP exhibits characteristics that are indicative of a developmentally significant protein, such as an early and restricted pattern of expression and the ability to mediate specific fiber-target interactions. A potential, selective adhesive mechanism by which LAMP may regulate the formation of specific circuits is investigated in the present experiments. LAMP is readily released from intact membranes by phosphatidyl inositol-specific phospholipase C. Purified, native LAMP, isolated by PI-PLC digestion and immunoaffinity chromatography, is capable of mediating fluorescent Covasphere aggregation via homophilic binding. To test the ability of LAMP to selectively facilitate substrate adhesion and growth of neurons from LAMP-positive, in contrast to LAMP-negative regions of the developing brain, purified LAMP was dotted onto nitrocellulose-coated dishes and test cells plated. Limbic neurons from perirhinal cortex bind specifically to substrate-bound LAMP within 4 hours, forming small cell aggregates with short neuritic processes that continue to grow through a 48 hour period of monitoring. Preincubation of cells with anti-LAMP has a modest effect on cell binding but significantly reduces initiation of process growth. Non-limbic neurons from somatosensory cortex and olfactory bulb fail to bind or extend processes on the LAMP substrate to any significant extent. All cell populations bind equally well and form neurites on poly-D-lysine and laminin. The present results provide direct evidence that LAMP can specifically facilitate interactions with select neurons in the CNS during development. The data support the concept that patterned expression of unique cell adhesion molecules in functionally related regions of the mammalian brain can regulate circuit formation.

Animals↗

PubMed1995

Age-dependent specification of the corticocortical connections of cerebral grafts.

To investigate further the factors involved in the development of cerebral cortical circuitry, we examined the organization of corticocortical connections of heterotopic grafts of fetal cortex placed into neonatal rat cortices. Presumptive perirhinal or sensorimotor areas of the cerebral wall were removed as slabs from embryonic day 12 (E12), E13, or E14 rats and transplanted heterotopically into either rostral perirhinal or sensorimotor cortical areas of neonatal rats. Two weeks later, the afferent cortical connections of the grafts were labeled by placing DilC18(-3) (Dil) into each transplant site. Both the E12 and E13 heterotopic transplants of presumptive perirhinal cortex contain mostly precursor cells. When these grafts are placed into sensorimotor cortex, callosal connections are formed primarily with the contralateral sensorimotor (Sml) area, the normal projection of Sml cortex. In contrast, the E14 heterotopic transplants of the perirhinal cortical wall, containing many more postmitotic neurons, developed contralateral connections with both sensorimotor and rostral perirhinal cortices. Thus, when precursor cells are transplanted heterotopically, by using E12/E13 donor tissue, the grafts receive projections that are similar to those of the host cortical area. When older cortical neurons, together with precursors, are transplanted into a heterotopic cortical area, by using E14 donor tissue, their cortical connections exhibit both host and original donor phenotypes. The data are consistent with our previous analysis of thalamocortical connections of grafts (Barbe and Levitt, 1992b) and suggest the existence of a cell-cell recognition system for thalamocortical and corticocortical circuit formation, whose mechanisms of action may be linked to the timing of neurogenesis.

Animals↗

PubMed1994

Involvement of protein kinase C in the axonal growth-promoting effect on spinal cord neurons by target-derived astrocytes.

Astroglial cells participate in a variety of developmental events during neuronal morphogenesis. We have shown that axonal, but not dendritic, outgrowth of spinal cord neurons can be promoted by a diffusible factor or factors secreted from target region-derived cerebellar astroglia in vitro in comparison with spinal astroglia. In the present study, we examined the involvement of protein kinase C (PKC) in the axon-promoting effect by astroglia. The inhibition of PKC by sphingosine or by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) at high concentration greatly reduced the mean axonal length of spinal neurons cultured in medium conditioned by cerebellar astroglia (SCn-CBg), while activation of PKC by TPA at low concentration, or by retinoic acid, was not additive to the glial effect. The activation of PKC by TPA or retinoic acid promoted axon growth of spinal neurons cultured in medium conditioned by spinal astroglia (SCn-SCg), which otherwise would not be as supportive for axon growth as cerebellar astroglia. Western blotting and PKC activity assays showed that there was a trend for increased PKC activity and protein levels (in particular, PKC beta) in SCn-CBg cultures, which correlated with enhanced axon growth. Inhibition of PKC by sphingosine appeared to decrease protein levels, especially PKC beta, which correlated with suppressed axon outgrowth. In SCn-SCg cultures, phorbol ester activation of PKC increased both activity and protein levels of both PKC alpha and PKC beta. This activation correlated with stimulated axonal outgrowth. These results suggest that the glial signaling that regulates specific axonal outgrowth by target astroglia is mediated in part by the PKC second messenger system.

Animals↗

PubMed1993

Immunocytochemical analysis of a novel carbohydrate differentiation antigen (CDA-3C2) associated with olfactory and otic systems during embryogenesis in the rat.

Carbohydrate differentiation antigens are known to display specific patterns of expression during mammalian development and are thought to participate in significant morphogenetic events. In the present study, two monoclonal antibodies that react with a novel carbohydrate differentiation antigen (CDA-3C2) were used to analyze, by light microscopy, the spatiotemporal distribution of this unique high molecular weight antigen during embryogenesis in the rat. Correlative analysis of the development of peripheral neural structures, in which CDA-3C2 was expressed, was carried out with an anti-neurofilament antibody. Enzymatic digestion, combined with Western blots, reveal that the CDA-3C2 epitope is a carbohydrate which is carried on a high molecular weight glycoprotein with a mass of greater than 1 million Daltons. Characteristic of carbohydrate antigens, immunoreactivity was found in several distinct cellular patterns: only along the apical border of cells, along lateral and basal membranes of cells, and extracellular-like staining in the mesenchyme. During neurulation, CDA-3C2 showed differential staining in the ectoderm, distinguishing lateral from neural regions. Following closure of the neural tube, there was a striking specificity of expression of CDA-3C2 in the periphery, found almost exclusively in olfactory and otic epithelial structures. While CDA-3C2 is found in placode-derived tissues that subserve sensory transduction, it appears to be primarily associated with the supportive cells (and their secretions) in both otic and olfactory regions and less so with the sensory cells. The data suggest that a unique carbohydrate antigen on a large macromolecule may play a role in neurulation and/or morphogenesis of the placode-derived otic and olfactory structures.

Animals↗

PubMed1993

Immunoelectron microscopic analysis of a novel carbohydrate differentiation antigen (CDA-3C2) in the developing rat olfactory and otic systems.

A carbohydrate differentiation antigen (CDA-3C2) exhibits a highly specific and restricted pattern of expression during rat embryogenesis. In the periphery of the embryo, this antigen is associated transiently with the lateral ectoderm but is retained only in the olfactory and otic epithelium throughout morphogenesis. At the light microscopic level, CDA-3C2 immunoreactivity appears mostly along cell periphery and in the extracellular matrix. The aim of the present study was to determine the specific cellular and subcellular distribution of CDA-3C2 in vivo in order to identify potential sites of cellular and tissue function of the antigen during embryogenesis. There was a strikingly similar subcellular distribution of CDA-3C2 in the developing otic and olfactory systems, found mostly along cell membranes, microvillar projections and acellular secretions of the epithelium. Mature sensory components of the epithelia were not immunoreactive, whereas supportive cells and their secreted structures were densely stained. The highly coincident nature of CDA-3C2 in both sensory epithelia suggests that this carbohydrate epitope, and possibly its carrier macromolecule, participate in a morphogenetic function common to these two sensory epithelia.

Animals↗

PubMed1993

Immunocytochemical demonstration of early appearing astroglial structures that form boundaries and pathways along axon tracts in the fetal brain.

During normal development of the mammalian forebrain, the paired cerebral hemispheres are initially separated midsagittally by the connective tissue-filled longitudinal fissure. During subsequent stages, the hemispheres fuse as basal lamina is remodeled and fibroblasts are eliminated from the fissure to create new central nervous system (CNS) territory in the midline. Two axon pathways, the corpus callosum and dorsal callosal stria, eventually use this region as part of their pathway. In order to assess the possible role of glial cells in the fusion process and in the guidance of axons in this and several other areas of the forebrain, we have analyzed the developing brain in timed cat and mouse embryos with immunohistochemical and morphological techniques. With the use of astroglial-specific antibodies and electron microscopy, we have visualized two distinct, primitive astroglial structures associated with the cerebral midline, and seven more associated with other specific brain regions. The way in which one of these structures moves as a column along the hemispheric midline in synchrony with seam formation suggests the possibility that during morphogenesis of the telencephalon, astrocytes may aid in the fusion process. In addition, the compact assemblage, early appearance and location of this and the other glial structures in relation to well defined neuroanatomical landmarks or axon pathways suggest that they may transiently compartmentalize relatively large regions of the CNS and organize certain developing fiber systems by acting as guides or barriers at critical stages of ontogeny.

Animals↗

PubMed1993

Establishment of vagal sensorimotor circuits during fetal development in rats.

The differentiation of vagal motor neurons and their emerging central relationship with vagal sensory afferents was examined in fetal rats. To identify peripherally projecting sensory and motor neurons, 1,1'-dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine perchlorate (DiI) was inserted into the proximal gut or cervical vagus nerve in fixed preparations. At embryonic day (E) 12, labeled vagal sensory neurons are present in the nodose ganglia and a few sensory axons project into the dorsolateral medulla. Central sensory processes become increasingly prevalent between E13 and E14 but remain restricted to the solitary tract. Vagal motor neurons are first labeled at E13, clustered within a region corresponding to the nucleus ambiguus (NA). Additional motor neurons appear to be migrating toward the NA from the germinal zone of the fourth ventricle. Motor neurons in the dorsal motor nucleus of the vagus (DMV) first project to the gut at E14 and have processes that remain in physical contact with the ventricular zone through E16. Sensory axons emerge from the solitary tract at E15 and project medially through the region of the nucleus of the solitary tract (NST) to end in the ventricular zone. A possible substrate for direct vagovagal, sensorimotor interaction appears at E16, when vagal sensory fibers arborize within the DMV and DMV dendrites extend into the NST. By E18, the vagal nuclei appear remarkably mature. These data suggest specific and discrete targeting of vagal sensory afferents and motor neuron dendrites in fetal rats and define an orderly sequence of developmental events that precedes the establishment of vagal sensorimotor circuits.

Animals↗

PubMed1993

Partial deafferentation of cat spinal neurons results in permanent changes in cell surface molecular expression and metabolic activity.

Partial denervation of spinal neurons often results in reactive reinnervation by spared systems and some recovery of function. Dorsal rhizotomy in the adult cat has been used for the examination of the molecular modifications that occur postsynaptically and which may underlie anatomical and behavioral plasticity. We examined two markers of postsynaptic neurons in the spinal cord. Immunolocalization of a specific marker of superficial dorsal horn and intermediolateral neurons, the limbic system-associated membrane protein (LAMP), revealed that removal of certain afferents results in a permanent decrease in LAMP expression. Cytochrome oxidase, a metabolic marker, is normally high in the neurons of Clarke's nucleus, but showed a dramatic decrease after deafferentation. Reactive reinnervation occurs in many regions of the spinal cord following partial deafferentation, including Clarke's nucleus and the dorsal horn, and these changes in presynaptic input may be manifest by permanent modifications in molecular expression and metabolic activity of spinal neurons.

Afferent Pathways↗

PubMed1993

Abdominal vagotomy dissociates the anorectic mechanisms for peripheral serotonin and cholecystokinin.

These studies compared the effects of total abdominal vagotomy (VGX) on ingestive actions produced by peripheral serotonergic and cholecystokinergic (CCKergic) stimulation in rats. Subcutaneous injection of 0.01-0.16 mumol/kg of the serotonin (5-HT) analogue 5-carboxamidotryptamine (5-CT) dose-dependently reduced mash intake equally in VGX rats and their laparotomized (LAP) controls but concurrently stimulated drinking only in the controls. The sulfated octapeptide of cholecystokinin (CCK-8, 4.0 nmol/kg ip) also reduced food intake only in the controls. In a second set of rats, vagotomy did not alter anorexia after intraperitoneal administration of either 2.0 or 8.0 mumol/kg of 5-HT or of 0.03 mumol/kg of 5-CT but abolished anorexia after a large dose of CCK-8 (8.0 nmol/kg). The completeness of vagotomy was verified histologically by immunohistochemical staining of the vagal bundles for the high molecular weight form of neurofilament-H protein. We report for the first time that 5-CT produces anorexia by a vagally independent mechanism. In contrast, 5-CT stimulates drinking by a pathway that does involve vagal function. Finally, we confirm the prediction that vagotomy dissociates the neural mechanisms for the anorectic action of peripheral 5-HTergic and CCKergic stimulation.

Abdomen↗

PubMed1993

Progressive acquisition of cortical phenotypes as a mechanism for specifying the developing cerebral cortex.

The formation of the cerebral cortex requires the assembly of a complex array of neurons that exhibit specific patterns of laminar distribution, connectivity, and macromolecular expression. The problem of how various areas become specified relies to a large extent on the ability to assay certain characteristics of a particular cortical area during development. Certain phenotypic features appear to be acquired early in histogenesis, whereas others have a relatively late onset of expression. This pattern of progressive acquisition of traits suggests that each feature may be regulated by a different set of genomic-environmental interactions. This would lead to an early framing of cortical regions through the commitment of cells to area-specific phenotypes, but allow modifications of later developing traits through changes in certain environmental features.

Animals↗

PubMed1992

Attraction of specific thalamic input by cerebral grafts depends on the molecular identity of the implant.

The cerebral cortex of mammals differentiates into functionally distinct areas that exhibit unique cytoarchitecture, connectivity, and molecular characteristics. Molecular specification of cells fated for limbic cortical areas, based on the expression of the limbic system-associated membrane protein (LAMP), occurs during an early period of brain development. The correlation between this early molecular commitment and formation of specific thalamocortical connections was tested by using a transplantation paradigm. We manipulated the phenotype of donor limbic and sensorimotor neurons by placing them in different cortical areas of host animals. Labeling of transplanted tissue with the lipophilic dye 1,1'-dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine was used to assay host thalamic neurons projecting to the donor tissue. We found that limbic thalamic axons successfully projected into cortical transplants (i) when LAMP was expressed by early committed limbic cortical neurons, irrespective of their host location, and (ii) when LAMP was expressed by uncommitted sensorimotor progenitor cells whose fate was altered by their new host locale. Thus, the response of cortical neurons to both intrinsic and environmental cues that influence their molecular phenotype has an important anatomical correlate, the development of specific patterns of thalamocortical connectivity.

Animals↗

PubMed1992

Temporal and spatial patterns of expression of laminin, chondroitin sulphate proteoglycan and HNK-1 immunoreactivity during regeneration in the goldfish optic nerve.

Current views suggest that the extracellular environment is critically important for successful axonal regeneration in the CNS. The goldfish optic nerve readily regenerates, indicating the presence of an environment that supports regeneration. An analysis of changes that occur during regeneration in this model may help identify those molecules that contribute to a favourable environment for axonal regrowth. We examined the distribution and expression of two extracellular matrix molecules, laminin and chondroitin sulphate proteoglycan, and a carbohydrate epitope shared by a family of adhesion molecules (HNK-1), using immunocytochemical detection in sections from the normal adult goldfish optic nerve and in nerves from one hour to five months following optic nerve crush. We also used in vitro preparations to determine if neurites in retinal explants could express these same molecules. The linear distributions of laminin and chondroitin sulphate proteoglycan immunoreactivity in control optic nerves are co-extensive with the glia limitans, suggesting both are expressed by non-neuronal components surrounding the axon fascicles. Between one and three weeks postoperatively when axons elongate and reach their target, laminin and chondroitin sulphate proteoglycan immunoreactivity increases around the crush site and distally. At six weeks postoperatively the pattern of immunoreactivity has returned to normal. While the temporal pattern of changes in immunoreactivity is similar, the spatial pattern of these two extracellular proteins in the regenerating nerve differs. Chondroitin sulphate proteoglycan immunoreactivity is organized in discrete columns associated with regenerating axons while laminin immunoreactivity is more diffusely distributed. Examination of retinal explants reveals growing neurites express chondroitin sulphate proteoglycan but not laminin. Our results suggest that laminin is only associated with non-neuronal cells, while chondroitin sulphate proteoglycan is associated with axons as well as non-neuronal cells. HNK-1 immunoreactivity is co-extensive with both the glia limitans and axon fascicles and is more extensively distributed in the intact nerve than either laminin or chondroitin sulphate proteoglycan immunoreactivity. In contrast to laminin and chondroitin sulphate proteoglycan, HNK-1 immunoreactivity is substantially decreased at the crush site within one week following optic nerve crush. HNK-1 immunoreactivity reappears through the crush site during the next several weeks, although non-immunoreactive regions, co-extensive with areas predominantly containing non-neuronal cells, persist both proximal and distal to the crush, up to six weeks postoperatively. The pattern suggests that HNK-1 epitope expression by these non-neuronal cells is decreased during axonal regeneration.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1992

Target-derived astroglia regulate axonal outgrowth in a region-specific manner.

The potential neuroanatomical specificity of astrocyte influence on neurite outgrowth was studied using an in vitro coculture system in which neurons from embryonic rat spinal cord or hippocampus were grown for 4 days in the presence of, but not in direct contact with, astrocytes derived either from the same region (homotopic coculture) or from different regions (heterotopic coculture) of the rat central nervous system. The results showed that axonal outgrowth was greatly enhanced in heterotopic cocultures in which spinal cord or hippocampal neurons were grown with astrocytes derived from their appropriate CNS target regions. This effect was remarkably specific, because the astroglia harvested from spinal or hippocampal target regions were not effective in promoting axon growth of nonafferent neuronal populations. Dendritic outgrowth was similar under all coculture conditions. These data suggest that diffusible signals, produced by astrocytes, can regulate neurite extension in vitro in a neuroanatomically specific manner and that axons are more sensitive than dendrites to the regional astrocyte environment.

Animals↗

PubMed1992

Myosin II distribution in neurons is consistent with a role in growth cone motility but not synaptic vesicle mobilization.

We have generated a polyclonal antibody against myosin II from a neuronally derived cell line in order to assess potential roles for myosin II in growth cone movement and synaptic transmission. The distribution of neuronal myosin II, in isolated cells as well as in tissues of the adult rat brain and spinal cord, was examined at the light microscopic and ultrastructural levels. In isolated neuroblastoma cells and dorsal root ganglion neurons, myosin II was found at the leading edge of growth cones, within neuritic processes and cell soma, and adjacent to the plasma membrane. The subcellular distribution of myosin II overlapped significantly with that of both actin and single-headed myosin I. These results implicate both myosin I and myosin II as molecular motors required for neurite elongation and growth cone motility. An exclusive postsynaptic distribution of myosin II in neurons of the mature central nervous system suggests that myosin II cannot play a role in the mobilization of synaptic vesicles, but could participate in synaptic plasticity.

Animals↗

PubMed1991

Differential immunochemical markers reveal the normal distribution of brain macrophages and microglia in the developing rat brain.

Brain macrophages and microglia play important roles in central nervous system (CNS) development, especially during regressive events in which particular neuronal and glial constituents are eliminated. The purpose of this study is to provide a complete map of brain macrophage and microglia distribution in all regions of the neuraxis from birth to sexual maturity. We have utilized morphology and immunostaining with the specific antibodies OX-42 and ED1 to distinguish between brain macrophages and microglia. Brain macrophages are large, round cells, 10-15 microns in diameter, with few or no cytoplasmic processes; these cells are ED1- and OX-42-immunopositive. Microglia have small cell bodies with numerous, ramified cytoplasmic processes. These cells are OX-42-positive, and ED1-negative. We found a specific pattern of distribution of brain macrophages, targeting specific cortical and subcortical areas transiently, including developing fiber tracts. These cells disappeared completely by the third postnatal week. In contrast, OX-42-positive microglia exhibited a gradual increase in number and were distributed uniformly throughout gray matter and within white matter tracts. These cells remain in the adult CNS, constituting the resident microglia population. We suggest that these two distinct phagocytic cell populations perform unique functions in the developing brain, including remodeling of restricted CNS areas by brain macrophages that is part of a normal morphological process.

Animals↗

PubMed1991

Brain macrophages and microglia respond differently to lesions of the developing and adult visual system.

Traumatic injury in the brain usually results in rapid degeneration of neuronal elements and a response by peripherally derived macrophages (brain macrophages, BMOs) and resident microglia. One intriguing result of lesions performed in the developing brain as compared to lesions of the mature brain is the faster resolution of the cellular debris and the absence of significant scarring. The purpose of this study was to examine the response of BMOs to induced cell death distant to the lesion site and to investigate possible differences in the responding phagocytic populations (BMOs versus microglia) following lesions in neonates and adults. Ablation of the visual cortex at birth results in very rapid retrograde degeneration and removal of neurons of the dorsal lateral geniculate nucleus (dLGN) within a few days. Lesions to the visual cortex of adult rats also induce neurons within the dLGN to die, but these cells do so over a much more protracted time course. Utilizing differences in morphology and immunocytochemical staining with the monoclonal antibodies ED1 and OX-42 to distinguish between BMOs and microglia, we found that in the developing CNS, BMOs are signalled rapidly and specifically to the location of induced cell death. Microglia are not involved in this response. As might be expected, the temporal response in the adult is much more protracted. In contrast to the developing brain, microglia and not macrophages are the predominant responding cell class after the adult lesion. The data suggest that these are distinct populations of phagocytic cells that respond to brain damage during development and in the adult, which may be critical in modulating the resolution and growth response after injury.

Animals↗