Article
Minocycline attenuates microglial activation but fails to mitigate degeneration in inferior olive and pontine nuclei after focal cerebellar lesion.
Santa Lucia Foundation I.R.C.C.S., Via del Fosso di Fiorano 65, 00143 Rome, Italy.
The Cerebellum (impact factor:
3.21).
08/2008;
7(3):401-5.
DOI:10.1007/s12311-008-0042-z
pp.401-5
Source: PubMed
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Citations (0)
- Cited In (2)
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Article: Past, present and future therapeutics for cerebellar ataxias.
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ABSTRACT: Cerebellar ataxias are a group of disabling neurological disorders. Patients exhibit a cerebellar syndrome and can also present with extra-cerebellar deficits, namely pigmentary retinopathy, extrapyramidal movement disorders, pyramidal signs, cortical symptoms (seizures, cognitive impairment/behavioural symptoms), and peripheral neuropathy. Recently, deficits in cognitive operations have been unraveled. Cerebellar ataxias are heterogeneous both at the phenotypic and genotypic point of view. Therapeutical trials performed during these last 4 decades have failed in most cases, in particular because drugs were not targeting a deleterious pathway, but were given to counteract putative defects in neurotransmission. The identification of the causative mutations of many hereditary ataxias, the development of relevant animal models and the recent identifications of the molecular mechanisms underlying ataxias are impacting on the development of new drugs. We provide an overview of the pharmacological treatments currently used in the clinical practice and we discuss the drugs under development.DNA research: an international journal for rapid publication of reports on genes and genomes 03/2010; 8(1):41-61. · 1.73 Impact Factor -
Article: Distinct regulation of nNOS and iNOS by CB2 receptor in remote delayed neurodegeneration.
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ABSTRACT: Hemicerebellectomy results in remote delayed degeneration of precerebellar neurons. We have reported that such a lesion induces type 2 cannabinoid receptor (CB(2)) expression in precerebellar neurons and that stimulation of CB(2), but not CB(1), has neuroprotective effects. In this study, we found that in the same model, the CB(2) agonist JWH-015 enhances neuronal nitric oxide synthase (nNOS) expression in axotomized neurons and that CB(2)-mediated neuroprotection is abrogated by pharmacological inhibition of nNOS. JWH-015 prevented the axotomy-induced upregulation of inducible NOS (iNOS) in astrocytes but had no effect on endothelial NOS (eNOS). In addition, we observed that JWH-015 significantly reduces hemicerebellectomy-induced neuroinflammatory responses and oxidative/nitrative stress. With regard to the signaling pathways of CB(2)/nNOS-mediated neuroprotection, we noted nNOS-dependent modulation of the expression of anti-oxidative (Hsp70) and anti-apoptotic (Bcl-2) proteins. These findings shed light on the interactions between the endocannabinoid and nitrergic systems after focal brain injury, implicating distinct functions of nNOS activation and iNOS inhibition in CB(2) signaling, which protect neurons from axotomy-induced cell death.Journal of Molecular Medicine 12/2011; 90(4):371-87. · 4.67 Impact Factor
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Keywords
areas remote
astrocytic response
axotomized precerebellar nuclei
central nervous system
cerebellar lesion
clinical outcome
CNS lesion
Degenerative changes
focal brain damage
Glial activation
influencing degenerative phenomena
microglial activations
mixed results
modulating inflammatory response
neuronal loss
primary lesion site
remote cell death
remote cell death phenomena
tetracycline derivative
Western blot techniques