Reactive Astrocyte Proliferation Research Articles

Type I Interferon Inhibits Astrocytic Gliosis and Promotes Functional Recovery after Spinal Cord Injury by Deactivation of the MEK/ERK Pathway

Formation of a glial scar is one of the major obstacles to axonal growth after injury to the adult CNS. In this study, we have addressed this issue by focusing on reactive astrocytes in a mouse model of spinal cord injury (SCI). First, we attempted to identify profile changes in the expression of astrocytic gliosis 10 days after injury by using gliosis-specific microdissection, genome-wide microarray, and MetaCore(trade mark) pathway analysis. This systematic data processing revealed many intriguing activated pathways. However, considering that proliferation/mitosis is one of the most prominent features of reactive astrocytes, we focused on the functional role of the Ras-MEK-ERK signaling cascades in reactive astrocytes. SCI-induced proliferation of reactive astrocytes in the lesion is in accordance with the increase in the expression and phosphorylation of MEK-ERK. Second, to reduce reactive gliosis after SCI, liposomes containing the interferon-beta (IFN-beta) gene were administered locally 30 min after injury. At 14 days after this treatment, GFAP-positive intensity and MEK-ERK phosphorylation at the lesion were reduced. In the animals receiving the IFN-beta gene, significant recovery of neurobehavior and parameters of electrophysiology following SCI was revealed by assessments of rotarod performance and improvements in the Basso Mouse Scale for locomotion and cortical motor-evoked potentials. SCI resulted in the degeneration of biotinylated dextran amine-labeled descending corticospinal tract axons, but the IFN-beta gene delivery induced regrowth of a large number of corticospinal tract axons. These results suggest that liposome-mediated IFN-beta gene delivery inhibits glial scar formation after SCI and promotes functional recovery.

The Basic Helix-Loop-Helix Transcription Factor Olig2 Is Critical for Reactive Astrocyte Proliferation after Cortical Injury

The mechanisms underlying the formation of the glial scar after injury are poorly understood. In this report, we demonstrate that after cortical injury Olig2 is upregulated in reactive astrocytes coincident with proliferation of these cells. Short-term lineage tracing studies with glial subtype-restricted transgenic reporter lines indicate that Olig2-expressing cells in the astroglial but not the oligodendroglial lineage are the essential source of reactive astrocytes. In addition, cortical Olig2 ablation results in a decrease in proliferation of reactive astrocytes in response to injury. Cell-type-specific mutagenesis indicates that Olig2 ablation in GFAP+ astrocytes and their precursors rather than in neuronal or oligodendroglial cells is responsible for the reduction of reactive astrocyte proliferation. Thus, our studies suggest that Olig2 is critical for postinjury gliosis.

Effect of olfactory ensheathing cells on reactive astrocytes in vitro.

Olfactory ensheathing cells have been used in several studies to promote repair in the injured spinal cord. However, cellular interaction between olfactory ensheathing cells and glial cells induced to be reactive in the aftermath of injury site has not been investigated. Using an in vitro model of astrogliosis, we show that reactive astrocytes expressed significantly less glial fibrillary acidic protein (GFAP) when cultured both in direct contact with olfactory ensheathing cells and when the two cell types were separated by a porous membrane. Immunofluorescence staining also suggested that reactive astrocytes showed decreased chondroitin sulfate proteoglycans in the presence of olfactory ensheathing cells, although the reduction was not statistically significant. No down-regulation of GFAP was observed when reactive astrocytes were similarly cultured with Schwann cells. Cell viability assay and bromodeoxyuridine uptake showed that proliferation of reactive astrocytes was significantly increased in the presence of olfactory ensheathing cells and Schwann cells.

Possible Role of P2Y2 Nucleotide Receptor in the Environment Generated After Injury

Spinal cord injury (SCI) increases inhibitory factors that may restrict neurite outgrowth after trauma. Release of inhibitory molecules and proliferation of reactive astrocytes at the injury site produce a nonpermissive environment for axonal regeneration. The mechanism that triggers astrogliosis is unknown, but the release of nucleotides has been linked to this hypertrophic state. Our goal is to investigate the spatio-temporal profile of P2Y2 after SCI. Molecular biology, immunohistochemical (IHC) studies, and behavioral assays were used to evaluate the expression and role of these receptors in rats injured at the T-10 level using the NYU impactor device. P2Y2 gene temporal profile using standardized RT-PCR showed a two-fold increase after 4–7 days post-injury (DPI) and returned to basal levels by 14 DPI. IHC studies demonstrated a low level of P2Y2 receptor in sham samples. After SCI, P2Y2 receptor expression in GFAP positive cells increased. Intrathecal infusion of suramin and PPADS antagonists resulted in some locomotor recovery. Our results suggest that P2Y2 receptors may play a role in the establishment of the restrictive environment for axonal regeneration after SCI. Supported by NIH-MRISP 2R2MH48190-14, NIH-SNRP NS39405, MBRS-SCORE S06-GM008224, MBRS-RISE GM-68138, PR-EPSCOR EPS-9874782.

Expression of multidrug resistance type 1 gene (MDR1) P-glycoprotein in intractable epilepsy with different aetiologies: a double-labelling and electron microscopy study

The objective of this study was to analyse the clinical characteristics, pathological features and expression patterns of multiple drug resistance type 1 (MDR1) and glial fibrillary acidic protein (GFAP) in intractable epilepsy patients with variable aetiologies and to analyse the relationships between the clinical and pathological findings. Twenty-six patients (15 males, 11 females, age range 4-25 years, mean age 22.92 years, SD 11.19 years) with intractable epilepsy were included in this study; the clinical characteristics were considered, and the pathological changes as well as expression of MDR1 and GFAP in surgically removed brain tissues of each subject were examined under light and electron microscopy. All patients presented a long-lasting, refractory epilepsy, mostly of the partial type, due to different causes, such as trauma, vascular injuries, encephalitis, cortical dysplasia, cavernous angioma and Sturge-Weber disease. Neuronal degenerative damage, reactive proliferation of astrocytes, as well as overexpression of GFAP and MDR1, appeared as common pathological features in all cases. The detection of MDR1 by electron microscopy allowed us to precisely define its cellular location in reactive astrocytes and to exclude the presence of the antigen in other cellular types. In all cases, pathological features, at both light and electron microscopy, were similar, independent of the different clinical presentation and aetiology.

Upregulation in astrocytic connexin 43 gap junction levels may exacerbate generalized seizures in mesial temporal lobe epilepsy

Following brain injury, and during the process of neurodegeneration, a reactive astrocytic proliferation occurs. This is accompanied by an increase in the synthesis of neuropeptides, cytokines, growth factors and glial fibrillary acidic protein (GFAP), a cell-specific marker for reactive astrocytes. Astrocytes are extensively coupled by gap junctions of the Cx43 connexin subtype. Several studies have shown that in severe trauma, coupling between astrocytes may add to the spread of the damaged area. In this study we ask whether the astrocytosis which is a feature of other neurodegenerative diseases also occurs in mesial temporal lobe epilepsy (MTLE) and whether it is accompanied by an increase in astrocytic communication through an upregulation of Cx43 gap junction channel proteins. In order to examine the astrocytic response and the expression pattern of Cx43 protein, double immunohistochemical labeling studies were undertaken using antibodies against GFAP and Cx43 applied to human hippocampal tissue resected from patients with MTLE, and to normal human control hippocampal tissue. Immunofluorescent labeling of astrocytes and Cx43 was examined using confocal laser scanning microscopy. The images obtained were quantitatively analysed and reconstructed using three-dimensional volume rendering. The results of this study have established that not only is astrocytosis greater in MTLE-affected tissues than previously suggested, but it is accompanied by a highly significant increase in astrocytic Cx43 protein levels. We hypothesize that this surprisingly large upregulation in Cx43 may exacerbate generalized seizures in the progression of MTLE.

An Update on Estrogen: Higher Cognitive Function, Receptor Mapping, Neurotrophic Effects

An Update on Estrogen: Higher Cognitive Function, Receptor Mapping, Neurotrophic Effects

7?-hydroxysterol is cytotoxic to neonatal rat astrocytes in primary culture when cAMP levels are increased

We have shown previously that 7beta-hydroxycholesterol (7betaOHCH) and 7beta-hydroxycholesteryl-3-oleate (7betaOHCH- 3-OL) are potent inhibitors of lesion-induced astrogliosis in the rat cortex or spinal cord; these substances reduce reactive astrocyte proliferation and hypertrophy. In this study, we employed cultured newborn rat astrocytes with increased cAMP levels as an in vitro model of reactive astrocytes. Treatment with either dibutyryl-cAMP (dbcAMP) or isoproterenol resulted in morphologic differentiation of astrocytes which became fibrous. Concomitant incubation with 30 microM 7betaOHCH and dbcAMP (or isoproterenol) provoked the cells to retract and was cytotoxic. When the beta-adrenergic receptor-mediated cAMP increase was abolished by propranolol, the 7betaOHCH cytotoxicity was inhibited. Immunocytochemical labelling for glial fibrillary acidic protein (GFAP) and beta-tubulin and electron microscopy suggested that intermediate filament and microtubular organizations were modified by 7betaOHCH. Analysis of the activity of cAMP-dependent protein kinase (PKA) in astrocytes treated with dbcAMP and 7betaOHCH showed a rapid and marked inhibition of the phosphotransferase activity which lasted for 24 hr. We suggest that this culture system provides an experimental system to study the molecular mechanisms involved in the effect of oxysterols on astrocytic hypertrophy. The cytotoxicity of 7betaOHCH seems to be mediated by inhibition of PKA, which phosphorylates intermediate filaments and the transcription factor cyclic AMP responsive element binding.

Deficiency of intercellular adhesion molecule 1 fails to mitigate selective neuronal death after transient global ischemia

Recent studies have shown a crucial role of intercellular adhesion molecule 1 (ICAM-1) in expansion of infarction after focal cerebral ischemia. The purpose of the present study was to assess whether ICAM-1 is involved in selective neuronal vulnerability and reactive gliosis after transient forebrain ischemia. ICAM-1 knockout mice and wild-type mice were subjected to transient forebrain ischemia for 5, 10 or 15 min, and the hippocampus and caudoputamen were examined 7 days later with conventional histological and immunohistochemical methods. Bilateral common carotid artery occlusion with less than 10% of baseline cortical microperfusion for 10 or 15 min resulted in ischemic neuronal damage in the hippocampus and caudoputamen. The frequency and the severity of neuronal damage were similar in wild-type and knockout mice. Proliferation of reactive astrocytes in the hippocampus was also similar in both types of mice. Therefore, it is highly unlikely that ICAM-1 plays a key role in delayed neuronal death after transient global ischemia or in astroglial responses after ischemic neuronal injury.

Novel Brain Ischemic Change on MRI

Specific change of persistent hyperintensity/hypointensity on T1-weighted (T1W) and T2-weighted (T2W) MRI, respectively, has been reported to develop in the human basal ganglia after brief hemispheric ischemia. We investigated whether this ischemic change observed in humans could be reproduced experimentally in rats after brief middle cerebral artery (MCA) occlusion (MCAO), and if so, what the neuroradiological change represented histologically. The origin of the right MCA of male Wistar rats (n=25) was occluded for 15 minutes by inserting a silicon-coated nylon thread from the external carotid artery into the internal carotid artery. After 15 minutes' MCAO, coronal MR images (T1W, T2W, and T1W with fat saturation pulse) were obtained once at 3-day reperfusion (n=5) and twice at 3- and 7-day reperfusion (n=20). Brain specimens were examined histologically immediately after the last MRI study in all rats. Neither T1W nor T2W MRI showed marked signal changes 3 days after reperfusion following 15-minute MCAO. However, the ischemic change of hyperintensity and hypointensity on T1W and T2W MRI, respectively, appeared in the striatum following 7-day reperfusion after 15-minute MCAO (n=19/20). Histological examination revealed that the specific lesion in the rat striatum on MRI corresponded to selective neuronal death and proliferation of reactive astrocytes and microglia without infarct, hemorrhage, lipid accumulation, or calcification. Brief MCAO with reperfusion induces the delayed ischemic changes of hyperintensity and hypointensity on T1W and T2W MRI, respectively, in the rat striatum with high reproducibility. This specific ischemic change on MRI histologically corresponded to selective neuronal death and gliosis with preservation of the macroscopic structure of the brain. A similar MRI pattern reported in patients who have sustained brief ischemia may represent similar histology. We speculate that the ischemic change reflects some biochemical changes affecting the magnetic field as the brain tissue undergoes subtle structural changes.

The effect of trapidil on the reactive astrocytic proliferation following spinal cord trauma in rats: Light and electron microscopic findings

Platelet-derived growth factor (POCF) released from platelets is one ofthe mitogens in serum, which plays a major role upon the cell biology, namely enhancing cell division and controlling of the maturation, especially upon the glial cell growth and its differentiation. Trapidil, which is an anti-POCF agent, inhibits the effect of POCF, especially the proliferative effects on the glial and tumoral cells in vitro. Previous studies suggested that the astrocytic proliferation stimulated by POCF was inhibited by trapidil via the selective antagonism. Trapidil was not found to have a considerable effect on the prevention of nonpermissive astrocytes in this study. It should be theorised that trapidil, administered immediately even after the trauma, could not reach the injury site in effective measure because of secondary events such as edema and impairment of blood circulation. This suggestion should be another subject for studies concerning trapidil which is administered prior to the trauma. [Neural Res 1998; 20: 365-373]

Increased neuronal cell survival after L-deprenyl treatment in experimental thiamine deficiency.

Experimental thiamine deficiency results in a reproducible pattern of selective neuronal cell death. Events such as blood-brain barrier breakdown, N-methyl-D-aspartic acid (NMDA) receptor-mediated excitotoxicity, and increased reactive oxygen species have been implicated in thiamine deficiency-induced neural loss. L-deprenyl protects dopaminergic, noradrenergic, and acetylcholinergic neurons from neurotoxic, mechanical, and excitotoxic damage. In the present study, the effects of l-deprenyl on neuronal cell survival were examined in rats made thiamine deficient by daily administration of the central thiamine antagonist pyrithiamine (0.5 mg/kg s.c.). Rats assigned to thiamine deficient or control groups received daily injections of l-deprenyl (0.25, 0.5, or 1.0 mg/kg/day i.p.) or vehicle until they reached a state of severe thiamine deficiency (loss of righting reflex). At this stage, thiamine status was restored by daily injections of thiamine (10 mg/kg s.c.) for 3 days, after which the animals were killed, and their brains were processed for neuronal cell counts (cresyl violet staining), astrocytic proliferation [glial fibrillary acidic protein (GFAP) immunohistochemistry], and monoamine oxidase B (MAO-B) activity. All rats receiving l-deprenyl (all doses) had significantly decreased neuronal cell loss in thalamic nuclei, in the inferior colliculus, and in the inferior olive and had a concomitant decrease in reactive astrocytic proliferation compared with the thiamine-deficient, vehicle-treated rats. The neuroprotective effects of l-deprenyl in thiamine deficiency induced brain damage most likely result from its properties other than its effects as an MAO-B inhibitor.

Increase of glial fibrillary acidic protein fragments in the spinal cord of motor neuron degeneration mutant mouse

We analyzed protein fractions extracted from the spinal cord of the motor neuron degeneration ( Mnd) mouse, a mutant that exhibits progressive degeneration of lower spinal motor neurons, by one- and two-dimensional polyacrylamide gel electrophoresis (PAGE) after solubilization of the tissue with medium containing sodium dodecyl sulfate (SDS)-urea during growth of the animal, in comparison with those of age-matched controls (C57BL/6). Several protein spots were detected around a region of p I 5.6–6.0 and molecular mass of 35–50 kDa in Mnd spinal cord tissue on the two-dimensional PAGE separation profile with Coomassie brilliant blue staining, while only a few spots around the same region were found in the control spinal cord. These spots were all immunoreactive with an antibody against glial fibrillary acidic protein (GFAP), a cytoskeleton filamentous protein specific to astroglial cells. The protein spot with molecular mass of 50 kDa showed immunoreactivity with anti-GFAP antibody, had a blocked amino-terminus, and is assumed to be intact GFAP. Several protein spots with slightly smaller molecular masses of 35 to 48 kDa lacked the head domain of the GFAP molecule as a result of cleavage at the 29th and 56th residues from the amino terminus. In Mnd spinal cord tissue, the densities of the immunoreactive GFAP bands with smaller molecular masses increased with development, and became dominant at the time of the appearance of behavioral paralytic gait around 6 to 7 months of age. These results suggest that the increased GFAPs devoid of head domains are related to the degenerative loss of motor neurons in the Mnd spinal cord. Histopathological and GFAP immunohistochemical examination of Mnd spinal cord preparation demonstrated progressive degenerative loss of motor neurons, and considerable increases in number of GFAP-stained astrocytes in the ventral horn at 7 to 9 months of age. These processes of degenerative loss of motor neurons and proliferation of reactive astrocytes with increased levels of fragmented GFAP in the Mnd spinal cord during development seem to be characteristic and preceded the deterioration of motor activities in this animal model of amyotrophic lateral sclerosis.

Intracerebral injection of interferon-gamma inhibits the astrocyte proliferation following the brain injury in the 6-day-old rat.

The present study examines the influence of interferon-gamma (IFN-gamma) on the astrocyte proliferation in the rat brain injured within the early period of postnatal development. Six-day-old male rats received a lesion in the left cerebral hemisphere and a single injection of recombinant rat IFN-gamma into the lesion cavity. One or 2 days after the injury the rats were injected with 3H-thymidine. Brain sections were immunostained for glial fibrillary acidic protein (GFAP), subjected to autoradiography, and examined microscopically to record proliferating GFAP-immunopositive astrocytes labeled with 3H-thymidine. In the IFN-gamma-injected rats, a statistically significant decrease in the intensity of reactive astrocyte proliferation was revealed. On day 1 after injury the intensity of astrocyte proliferation showed dose-dependent changes. Relations between the astrocyte reactivity and multiple factors existing in the injured and IFN-gamma-injected brain are discussed. The results represent the first in vivo evidence of a dose-dependent action of IFN-gamma on the astrocyte proliferation in response to injury.

Intracerebral injection of interferon‐gamma inhibits the astrocyte proliferation following the brain injury in the 6‐day‐old rat

The present study examines the influence of interferon-gamma (IFN-γ) on the astrocyte proliferation in the rat brain injured within the early period of postnatal development. Six-day-old male rats received a lesion in the left cerebral hemisphere and a single injection of recombinant rat IFN-γ into the lesion cavity. One or 2 days after the injury the rats were injected with 3H-thymidine. Brain sections were immunostained for glial fibrillary acidic protein (GFAP), subjected to autoradiography, and examined microscopically to record proliferating GFAP-immunopositive astrocytes labeled with 3H-thymidine. In the IFN-γ-injected rats, a statistically significant decrease in the intensity of reactive astrocyte proliferation was revealed. On day 1 after injury the intensity of astrocyte proliferation showed dose-dependent changes. Relations between the astrocyte reactivity and multiple factors existing in the injured and IFN-γ-injected brain are discussed. The results represent the first in vivo evidence of a dose-dependent action of IFN-γ on the astrocyte proliferation in response to injury. J. Neurosci. Res. 50:1018–1022, 1997. © 1997 Wiley-Liss, Inc.

Long-term postnatal effect of prenatal irradiation on the astrocyte proliferative response to brain injury

Pregnant Wistar rats were exposed to a single 1.0 Gy dose of γ-irradiation on gestational day 13, 15, 17 or 19. Thirty-day-old male offspring received a mechanical lesion in the left cerebral hemisphere. One, 2 or 4 days after the injury the rats were injected with [ 3H]thymidine and sacrificed 4 h after the injection. Thereafter, brain sections were immunostained for GFAP or S100 β protein, subjected to autoradiography and examined microscopically to record immunopositive astrocytes labelled with [ 3H]thymidine. Statistically significant elevation of the reactive astrocyte proliferation was revealed on the 2nd day following injury in brains irradiated on gestational day 15. The results represent the first in vivo evidence that a low-dose prenatal γ-irradiation can induce a long-term increase in the ability of astroglia to proliferate in response to injury.

Effect of oxysterol treatment on cholesterol biosynthesis and reactive astrocyte proliferation in injured rat brain cortex.

We have reported previously that oxysterols inhibit astrogliosis and intracranial glioblastoma growth. To elucidate the mechanism of action of these molecules in vivo, we have investigated their effect on the cholesterol biosynthesis in the injured brain. In a bilateral lesion model, injection of liposomes containing 7 beta-hydroxy-cholesterol decreased [3H]acetate incorporation into neutral lipids and cholesterol by 30% and 40%, respectively. Structural analogues were tested using a unilateral lesion model. The injury did not significantly affect cholesterogenesis; injection of 7 beta-hydroxycholesterol or 7 beta-hydroxycholesteryl-3-oleate reduced acetate incorporation into cholesterol by 47% and 43%, respectively. Both 7-ketocholesteryl-3-oleate and 7 alpha-hydroxycholesteryl-3-oleate inhibited cholesterogenesis by 32%. As cholesterol and by-products of the cholesterol pathway play a key role in cell division, we have assessed the effect of oxysterols on reactive astrocyte proliferation. The incorporation of bromodeoxyuridine showed that up to 46% of astrocytes were proliferating 24 h after the injury. Injection of 12 nmol of 7 beta-hydroxycholesterol or 7 beta-hydroxycholesteryl-3-oleate reduced the labelling index to 26%, whereas the labelling index in the 7-keto-cholesteryl-3-oleate-treated cortex was 37%. These findings demonstrate that oxysterols are potent inhibitors of the endogenous cholesterol biosynthesis in brain and show a correlation between cholesterogenesis and reactive astrocyte proliferation.

Depolarization-induced acid secretion in gliotic hippocampal slices

Gliotic hippocampal slices were used to study glial acid secretion in a tissue largely devoid of neural elements. Rat hippocampal slices were prepared 10–28 days after sterotaxic injection of kainate. Cresyl Violet staining and immunohistochemistry for glial fibrillary acidic protein demonstrated a loss of neurons and a proliferation of reactive astrocytes in area CA3. Extracellular pH and K + shifts were recorded in CA3 in response to K + iontophoresis. Elevation of K + evoked an extracellular acid shift that was two- to three-fold larger in gliotic versus unlesioned tissue. Ba 2+ caused a slow extracellular acidification, and blocked both the depolarizing responses of the glial cells and the acid shifts evoked by K +. The K +-evoked acid shifts were abolished in Na +-free media, and diminished in HEPES-buffered solutions. Inhibition of extracellular carbonic anhydrase caused a reversible enhancement of the K +-evoked acid shifts, an effect that could be mimicked during H + iontophoresis in agarose gels. Gliotic acid shifts were unaffected by amiloride or its analogs, stilbenes, zero Cl − media, zero or elevated glucose, lactate transport inhibitors, zero Ca 2+ or Cd 2+. Smaller acid shifts could be evoked in normal slices which were also enhanced by benzolamide, and blocked by Ba 2+ and zero Na + media. It is concluded that acid secretion by reactive astrocytes is Na + and HCO 3 ∼-dependent and is triggered by depolarization. The similar pharmacological and ionic sensitivity of the acid shifts in non-gliotic tissue suggest that these properties are shared by normal astrocytes. These characteristics are consistent with the operation of an electrogenic Na +-HCO 3 − co-transporter. However, the enhancement of the acid shifts by inhibitors of extracellular carbonic anhydrase suggests that CO 3 2− rather than HCO 3 −, is the transported acid equivalent.

Stimulation of reactive astrogliosis in vivo by extracellular adenosine diphosphate or an adenosine A2 receptor agonist

Adenosine and its nucleotides adenosine triphosphate (ATP) and adenosine diphosphate (ADP) stimulate the proliferation of brain astrocytes in vitro and augment the effects of other growth factors. Following brain injury, hypoxia, or around solid tumors with necrotic centers, such as glioblastoma multiformes, high concentrations of adenine nucleotides and adenosine are released into the extracellular space; extracellular adenosine concentrations can rise 30-100-fold to a concentration in excess of 100 microM. Increased concentrations of extracellular adenosine and adenine nucleotides may contribute to reactive astrocytic proliferation following brain injury. To test this hypothesis, adenosine, an adenosine analog 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA), or ADP was micro-injected into rat cortex. The number of glial fibrillary acidic protein-immunopositive cells was compared between the treated and contralateral saline-injected hemispheres. Within 48 hr, astrocyte density around the CPCA (100 microM) infusion site was almost double that around the control saline infusion site. In hemispheres into which CPCA was infused, there was an increase in astrocytes in the subpial region along fiber tracts and around blood vessels, characteristic of Scherer's secondary structures found in association with malignant astrocytic brain tumors. The increased astrogliosis elicited by CPCA was abolished by coinfusion of the adenosine A2 receptor antagonist 1,3-dipropyl-7-methylxanthine (DPMX). While microinjection of adenosine (1 mM) failed to stimulate astrogliosis, microinjection of ADP (500 microM) also resulted in a significant reactive astrogliosis and accumulation of astrocytes similar to Scherer's secondary structures.(ABSTRACT TRUNCATED AT 250 WORDS)

A neuropathological study of a case of lupus erythematosus with chorea

Neuropathological examination in a 48-year-women of SLE with chorea was performed. Histological examination of the putamen showed a widespread neuronal loss associated with reactive astrocyte proliferation and neuropil rarefaction at both sides. Disappearance of large neurons was more prominent than that of small ones. Although a few old and fresh microinfarcts were scattered in the same area, there was no significant pathological abnormality in small vessels. The caudate nuclei also showed a few irregular microinfarcts and spotty loss of neurons associated with reactive astrocytosis. These neuropathological changes might be related to the appearance of choreatic movement in patients with SLE.