Molecular neurobiology
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Molecular neurobiology · Dec 2018
ReviewExosomes in Acquired Neurological Disorders: New Insights into Pathophysiology and Treatment.
Exosomes are endogenous nanovesicles that play critical roles in intercellular signaling by conveying functional genetic information and proteins between cells. Exosomes readily cross the blood-brain barrier and have promise as therapeutic delivery vehicles that have the potential to specifically deliver molecules to the central nervous system (CNS). This unique feature also makes exosomes attractive as biomarkers in diagnostics, prognostics, and therapeutics in the context of multiple significant public health conditions, including acquired neurological disorders. ⋯ In total, ten research articles were identified that examined exosomes in the context of TBI, SCI, or stroke; these manuscripts were reviewed and synthesized to further understand the current role of exosomes in the context of acquired neurological disorders. Of the ten published studies, four focused exclusively on TBI, one on both TBI and SCI, and five on ischemic stroke; notably, eight of the ten studies were limited to pre-clinical samples. The present review is the first to discuss the current body of knowledge surrounding the role of exosomes in the pathophysiology, diagnosis, and prognosis, as well as promising therapeutic strategies in TBI, SCI, and stroke research.
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Molecular neurobiology · Dec 2018
2-Pentadecyl-2-Oxazoline Reduces Neuroinflammatory Environment in the MPTP Model of Parkinson Disease.
Current pharmacological management of Parkinson disease (PD) does not provide for disease modification, but addresses only symptomatic features. Here, we explore a new approach to neuroprotection based on the use of 2-pentadecyl-2-oxazoline (PEA-OXA), the oxazoline derivative of the fatty acid amide signaling molecule palmitoylethanolamide (PEA), in an experimental model of PD. Daily oral treatment with PEA-OXA (10 mg/kg) significantly reduced behavioral impairments and neuronal cell degeneration of the dopaminergic tract induced by four intraperitoneal injections of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on 8-week-old male C57 mice. ⋯ PEA-OXA treatment also diminished nuclear factor-κB traslocation, cyclooxygenase-2, and inducible nitric oxide synthase expression and through upregulation of the nuclear factor E2-related factor 2 pathway, induced activation of Mn-superoxide dismutase and heme oxygenase-1. Further, PEA-OXA modulated microglia and astrocyte activation and preserved microtubule-associated protein-2 alterations. In conclusion, pharmacological activation of nuclear factor E2-related factor 2 pathways with PEA-OXA may be effective in the future therapy of PD.
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Molecular neurobiology · Dec 2018
Elevation of MMP-9 Levels Promotes Epileptogenesis After Traumatic Brain Injury.
Posttraumatic epilepsy (PTE) is a recurrent seizure disorder that often develops secondary to traumatic brain injury (TBI) that is caused by an external mechanical force. Recent evidence shows that the brain extracellular matrix plays a major role in the remodeling of neuronal connections after injury. One of the proteases that is presumably responsible for this process is matrix metalloproteinase-9 (MMP-9). ⋯ MMP-9 knockout mice exhibited the opposite response profile. Finally, we found that the occurrence of PTE was correlated with the size of the lesion after injury. Overall, our data emphasize the contribution of MMP-9 to TBI-induced structural and physiological alterations in brain circuitry that may lead to the development of PTE.