Search results for "Neuroprotective agents"
showing 10 items of 153 documents
Early-onset tolerance in rat global cerebral ischemia induced by a mitochondrial inhibitor
2000
It was studied whether a subtoxic dose of the mitochondrial neurotoxin, 3-nitropropionic acid (3-NPA), can initiate early-onset tolerance induction for subsequent ischemic injury. Wistar rats were pretreated for 3 h by intraperitoneal 3-NPA (20 mg/kg body weight; n=13) or solvent (n=12). Fifteen minutes global cerebral ischemia was induced by bilateral carotid artery occlusion and hypobaric hypotension. rCBF and tissue hemoglobin oxygen saturation were measured by laser Doppler scanning and a microspectrophotometric method. Ischemic insult and brain temperature were identical in both groups. Body weight and neurological scores recovered in the pretreated group but further deteriorated in th…
Pioglitazone Reduces Secondary Brain Damage after Experimental Brain Trauma by PPAR-γ-Independent Mechanisms
2011
Inflammatory and ischemic processes contribute to the development of secondary brain damage after mechanical brain injury. Recent data suggest that thiazolidinediones (TZDs), a class of drugs approved for the treatment of non-insulin-dependent diabetes mellitus, effectively reduces inflammation and brain lesion by stimulation of the peroxisome proliferator-activated receptor-γ (PPAR-γ). The present study investigates the influence of the TZD pioglitazone and rosiglitazone on inflammation and secondary brain damage after experimental traumatic brain injury (TBI). A controlled cortical impact (CCI) injury was induced in male C57BL/6 mice to investigate following endpoints: (1) mRNA expression…
Amphiphilic polyaspartamide copolymer-based micelles for rivastigmine delivery to neuronal cells
2012
A novel polysorbate-80 (PS(80))-attached amphiphilic copolymer comprising a hydrophilic α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) backbone and hydrophobic squalenyl-C(17) (Sq(17)) portions was synthesized and characterized; the formation of polymeric micelles was also evaluated. Rivastigmine free-base (Riv), a hydrophobic drug employed to treat Alzheimer's disease, was chosen as model drug to investigate micelle's ability to incorporate hydrophobic molecules and target them to neuronal cells. Micelle formation was studied through analyses including fluorescence spectroscopy and 2D (1)H-NMR NOESY experiments. Finally, the capacity of Riv-loaded micelles, versus free drug, to penetrat…
Inhalational or intravenous anesthetics for craniotomies? Pro inhalational.
2006
In neurosurgery, anesthesiologists and surgeons focus on the same target - the brain. The nature of anesthetics is to interact with brain physiology, leading to favorable and adverse effects. Research in neuroanesthesia over the last three decades has been dedicated to identifying the optimal anesthetic agent to maintain coupling between cerebral blood flow and metabolism, keep cerebrovascular autoregulation intact, and not increase cerebral blood volume and intracranial pressure.Sevoflurane is less vasoactive than halothane, enflurane, isoflurane, or desflurane. The context sensitive half-life is short and similar to that of desflurane, which translates into fast on and offset. Compared wi…
Indicaxanthin, a multi-target natural compound from Opuntia ficus-indica fruit: From its poly-pharmacological effects to biochemical mechanisms and m…
2019
Abstract Over the latest years phytochemical consumption has been associated to a decreased risk of both the onset and the development of a number of pathological conditions. In this context indicaxanthin, a betalain pigment from Opuntia ficus-indica fruit, has been the object of sound research. Explored, at first, for its mere antioxidant potential, Indicaxanthin is now regarded as a redox-active compound able to exert significant poly-pharmacological effects against several targets in a number of experimental conditions both in vivo and in vitro. This paper aims to provide an overview on the therapeutical effects of indicaxanthin, ranging from the anti-inflammatory to the neuro-modulatory…
Neuronal injury in chronic CNS inflammation.
2010
Introduction Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system which is characterized by inflammatory demyelination and neurodegeneration. Neurological symptoms include sensory disturbances, optic neuritis, limb weakness, ataxia, bladder dysfunction, cognitive deficits and fatigue. Pathophysiology The inflammation process with MS is promoted by several inflammatory cytokines produced by the immune cells themselves and local resident cells like activated microglia. Consecutive damaging pathways involve the transmigration of activated B lymphocytes and plasma cells, which synthesize antibodies against the myelin sheath, boost the immune atta…
Neurodegeneration in multiple sclerosis: novel treatment strategies.
2012
In recent years it has become clear that the neuronal compartment already plays an important role early in the pathology of multiple sclerosis (MS). Neuronal injury in the course of chronic neuroinflammation is a key factor in determining long-term disability in patients. Viewing MS as both inflammatory and neurodegenerative has major implications for therapy, with CNS protection and repair needed in addition to controlling inflammation. Here, the authors' review recently elucidated molecular insights into inflammatory neuronal/axonal pathology in MS and discuss the resulting options regarding neuroprotective and regenerative treatment strategies.
Beta-amyloid monomers are neuroprotective
2009
The 42-aa-long β-amyloid protein—Aβ1-42—is thought to play a central role in the pathogenesis of Alzheimer's disease (AD) (Walsh and Selkoe, 2007). Data from AD brain (Shankar et al., 2008), transgenic APP (amyloid precursor protein)-overexpressing mice (Lesné et al., 2006), and neuronal cultures treated with synthetic Aβ peptides (Lambert et al., 1998) indicate that self-association of Aβ1-42monomers into soluble oligomers is required for neurotoxicity. The function of monomeric Aβ1-42is unknown. The evidence that Aβ1-42is present in the brain and CSF of normal individuals suggests that the peptide is physiologically active (Shoji, 2002). Here we show that synthetic Aβ1-42monomers support …
The Role of Erythropoietin in Neuroprotection: Therapeutic Perspectives
2007
Nervous system diseases are very complex conditions comprising a large variety of local and systemic responses. Several therapeutic agents interfering with all or in part the biochemical steps that ultimately cause neuronal death have been demonstrated to be neuroprotective in preclinical models. However, all the agents so far investigated have inexorably failed in the phase III trials carried out. A large body of evidence suggests that the hormone erythropoietin (EPO), besides its well-known hematopoietic action, exerts beneficial effects in the central nervous system. EPO's effect has been assessed in several experimental models of brain and spinal cord injury thus becoming a serious cand…
Mildronate and its neuroregulatory mechanisms: targeting the mitochondria, neuroinflammation, and protein expression.
2013
This review for the first time summarizes the data obtained in the neuropharmacological studies of mildronate, a drug previously known as a cardioprotective agent. In different animal models of neurotoxicity and neurodegenerative diseases, we demonstrated its neuroprotecting activity. By the use of immunohistochemical methods and Western blot analysis, as well as some selected behavioral tests, the new mechanisms of mildronate have been demonstrated: a regulatory effect on mitochondrial processes and on the expression of nerve cell proteins, which are involved in cell survival, functioning, and inflammation processes. Particular attention is paid to the capability of mildronate to stimulate…