ABSTRACT
Mild cognitive impairment (MCI) is defined as inter-stage between normal cognitive aging and major neurocognitive disorder (MND). This state of decay is a crucial factor in treatment to prevent the progression to MND. In this study, our group developed a virtual screening process to evaluate 2568 phytochemical compounds against 5 key proteins associated with MCI and MND. As a result, two potential candidates were identified: carpaine, found in Carica papaya leaves, and punicalagin, present in Punica granatum. A model of cognitive impairment (CI) was developed in 10-month-old male Sprague Dawley rats by administering aluminum chloride (AlCl3) at a dose of 100 mg/kg/day for 30 days. After AlCl3 administration period, one of the groups received carpaine and punicalagin in a phytochemical extract (PE) by oral gavage for 30 days. Novel object recognition test (NOR) was assessed at three different time points (T1 - before CI, T2 - after CI, and T3 - after PE treatment). Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were identified in the hippocampus of rats at the end of the study period. After administration of AlCl3, a reduction in discrimination index vs control rats (CI = 0.012 ± 0.08 vs Control = 0.076 ± 0.03), was observed. After phytochemical extract treatment, a significant increase in discrimination index values was observed in the PE group 0.4643 ± 0.13 vs CI group 0.012 ± 0.08. Additionally, the evaluation of immunohistochemistry showed an increase in GFAP positivity in the hippocampus of the CI groups, while a slight decrease was observed in the PE group. This work addressed a comprehensive methodology that utilized in silico tools to identify phytochemical compounds (carpaine and punicalagin) as potential candidates for affecting key proteins in CI. The phytochemical extract containing carpaine and punicalagin resulted in a trend in the decrease of GFAP expression in the hippocampus and improved recognition memory in rats with CI induced by age and AlCl3 administration.
Subject(s)
Carica , Cognitive Dysfunction , Hydrolyzable Tannins , Pomegranate , Mice , Rats , Male , Animals , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Carica/chemistry , Disease Models, Animal , Rats, Sprague-Dawley , Cognitive Dysfunction/drug therapy , Phytochemicals , SeedsABSTRACT
Traumatic spinal cord injury (TSCI) can cause paralysis and permanent disability. Rehabilitation (RB) is currently the only accepted treatment, although its beneficial effect is limited. The development of biomaterials has provided therapeutic possibilities for TSCI, where our research group previously showed that the plasma-synthesized polypyrrole/iodine (PPy/I), a biopolymer with different physicochemical characteristics than those of the PPy synthesized by conventional methods, promotes recovery of motor function after TSCI. The present study evaluated if the plasma-synthesized PPy/I applied in combination with RB could increase its beneficial effects and the mechanisms involved. Adult rats with TSCI were divided into no treatment (control); biopolymer (PPy/I); mixed RB by swimming and enriched environment (SW/EE); and combined treatment (PPy/I + SW/EE) groups. Eight weeks after TSCI, the general health of the animals that received any of the treatments was better than the control animals. Functional recovery evaluated by two scales was better and was achieved in less time with the PPy/I + SW/EE combination. All treatments significantly increased ßIII-tubulin (nerve plasticity) expression, but only PPy/I increased GAP-43 (nerve regeneration) and MBP (myelination) expression when were analyzed by immunohistochemistry. The expression of GFAP (glial scar) decreased in treated groups when determined by histochemistry, while morphometric analysis showed that tissue was better preserved when PPy/I and PPy/I + SW/EE were administered. The application of PPy/I + SW/EE, promotes the preservation of nervous tissue, and the expression of molecules related to plasticity as ßIII-tubulin, reduces the glial scar, improves general health and allows the recovery of motor function after TSCI. The implant of the biomaterial polypyrrole/iodine (PPy/I) synthesized by plasma (an unconventional synthesis method), in combination with a mixed rehabilitation scheme with swimming and enriched environment applied after a traumatic spinal cord injury, promotes expression of GAP-43 and ßIII-tubulin (molecules related to plasticity and nerve regeneration) and reduces the expression of GFAP (molecule related to the formation of the glial scar). Both effects together allow the formation of nerve fibers, the reconnection of the spinal cord in the area of injury and the recovery of lost motor function. The figure shows the colocalization (yellow) of ßIII-tubilin (red) and GAP-43 (green) in fibers crossing the epicenter of the injury (arrowheads) that reconnect the rostral and caudal ends of the injured spinal cord and allowed recovery of motor function.
Subject(s)
Biocompatible Materials , Exercise Therapy/methods , Iodine/chemistry , Polymers/chemistry , Pyrroles/chemistry , Spinal Cord Injuries/rehabilitation , Spinal Cord Injuries/surgery , Animals , Argon Plasma Coagulation/methods , Biocompatible Materials/administration & dosage , Biocompatible Materials/chemical synthesis , Biocompatible Materials/chemistry , Biocompatible Materials/radiation effects , Chemical Precipitation/radiation effects , Combined Modality Therapy , Disease Models, Animal , Environment Design , Female , Injections, Spinal , Iodine/administration & dosage , Iodine/radiation effects , Laminectomy , Lasers, Gas/therapeutic use , Motor Activity/drug effects , Motor Activity/physiology , Nerve Regeneration/drug effects , Nerve Regeneration/physiology , Polymers/administration & dosage , Polymers/chemical synthesis , Polymers/radiation effects , Pyrroles/administration & dosage , Pyrroles/chemical synthesis , Pyrroles/radiation effects , Rats , Rats, Long-Evans , Recovery of Function/drug effects , Recovery of Function/physiology , Spinal Cord Injuries/pathology , Spinal Cord Regeneration/drug effects , SwimmingABSTRACT
Spinal cord injury (SCI) is a condition that puts the patient's life at risk in the acute phase and, during the chronic stage, results in permanent deficits in motor, sensory and autonomic functions. Isolated therapeutic strategies have not shown an effect on this condition. Therefore, this study aimed to evaluate the effects of electroacupuncture (EA) and curcumin, alone or combined, on the oxidative balance, motor function recovery and amount of preserved tissue following a traumatic SCI. Long-Evans rats were divided into five groups: SHAM, SCI, SCI + EA, SCI + Curcumin, and SCI + EA + Curcumin. Nitric oxide was significantly decreased in the Curcumin group; the EA, Curcumin and SCI + EA + Curcumin groups had significantly decreased hydroxyl radical and lipid peroxidation levels. Motor function recovery and the amount of preserved spinal cord tissue were significantly greater in the EA, Curcumin and EA + Curcumin groups. The results show that EA and Curcumin treatment alone or in combination decreased oxidative stress, improved functional motor recovery and increased the amount of preserved spinal cord tissue following a traumatic injury.