The Neuro Engraftment and Neuroregenerative effects of Hydrogen Sulphide Donor, Intracerebral MSCs, Ginko Biloba and Kefir in Attenuating Neuropathological hallmarks of Lipopolysaccharide induced Alzheimer’s disease Rat models

Abstract

Background: Memory disorders have been characterized by being a devastating long term incurable diseases with a huge social impact in addition to a diminished efficient available medical treatments. Deep Brain stimulation via using neuroprotective inducers for treatment of brain structure degenerative diseases such as Alzheimer's disease (AD) can be considered as being a promising successful therapy due to its various targets and underlying mechanisms for improving brain dysfunction. Objectives: The main aim of this study is to suggest therapeutic protocol having the potentials for restoring normal neurons diverse population and modifying neuropathological deposited hallmarks including both positive and negative lesions. Materials and Methods: Rats were divided into nine groups: (G1) control ;(G2) rats received LPS as a method of inducing nongenetically manipulated AD;(G3)AD rats received NaHS;(G4) AD rats received MSCs intracerebrally;(G5) AD rats received MSCs+NaHS;(G6)AD rats received kefir+GB;(G7)AD rats received MSCs+kefir+GB;(G8)AD rats received NaHS+kefir+GB; (G9) AD rats received MSCs+NaHS+kefir+GB. Results: AD induction resulted in down-regulation of CBS expression and GSH brain tissue level accompanied with overexpression in amyloid-β protein, MAPK, tau protein, ACAT expression and MDA brain tissue level in addition to elevated caspase-3 serum level. Conclusion: The implantation of amyloid reliving therapy that do have a wide clinical impact if initiated at benign plaques stage before irreversible brain damage occurs. The following effects have been observed following the administration of suggested medical protocol where a decrease in AD pathological deposited hallmarks has been observed with maintaining inflammatory brain factors by functioning as a potent neuroregenerative.

The emerging mechanism behind viral infections and extracellular vesicles hypotheses leading to neuroinflammation and Alzheimer's disease pathology

“…Once reaching the CNS, the virus directly begins to replicate along with the release of pathogen‐associated molecular patterns (PAMPs) and damage‐associated molecular patterns (DAMPs) leading to lipopolysaccharides (LPS) like effects. 35 , 36 , 37 , 38 , 39 , 40 Consequently, this results in the activation and release of pro‐inflammatory cytokines, chemokines, and reactive oxygen species (ROS) associated with TNF‐α and NF‐kB. Ultimately, wide exaggerated immune responses against HSV‐1 are characterized by aggressive inflammatory responses and the activation of M1 microglia type leading to AD.…”

The role of extracellular matrix alterations in mediating astrocyte damage and pericyte dysfunction in Alzheimer's disease: A comprehensive review

“…Additionally, neuronal damage can act as a potential triggering factor for the fragmentation of CSPGs, which function as a toxic damage associated-molecular pattern (DAMP) (Bianchi, 2007;Castillo et al, 1998). It was previously reported that these toxic DAMP fragments directly bind to toll-like receptors (TLRs), initiating several proinflammatory cascades, activating reactive astrocytes/microglia cells, and exaggerating the release of nitric oxide (NO), IL-1β, IL-6, and TNF-α (Anwar, 2019;Anwar et al, 2018Anwar et al, , 2019aAnwar et al, , 2019bGorina et al, 2011;Pedrazzi et al, 2007;Ponath et al, 2007;Siebert et al, 2014). Therewith, activation of phosphoinositide 3-kinases (PI3K)/protein kinase-B (AKT), nuclear-factor-κB (NFκB), and mitogen-activated protein kinase (MAPK) signaling pathways results in the aggregation of Aβ plaques in the brain (Anwar et al, 2018;Bianchi, 2007;Castillo et al, 1998;Gorina et al, 2011;Lau et al, 2012;Siebert et al, 2014).…”

“…The exaggerated release of these proinflammatory cytokines may contribute to ECM inflammation and degradation, ending with blood-brain barrier (BBB) damage in addition to brain atrophy tissues. These toxic depositions among brain tissue result in the activation of TLR-4, leading to the production of more toxic neuroinflammatory cytokines (Anwar et al, 2019a(Anwar et al, , 2019b. Following the activation of TLR-4, which was previously proven to responsible for AD and oligodendrocyte damage contributing to brain atrophy (Anwar et al, 2018(Anwar et al, , 2019a(Anwar et al, , 2019b, an increase in the expression of IL-1ß, IL-6, and TNF-α within the brain was reported (Anwar et al, 2018(Anwar et al, , 2019a(Anwar et al, , 2019b (Figure 3).…”

“…These toxic depositions among brain tissue result in the activation of TLR-4, leading to the production of more toxic neuroinflammatory cytokines (Anwar et al, 2019a(Anwar et al, , 2019b. Following the activation of TLR-4, which was previously proven to responsible for AD and oligodendrocyte damage contributing to brain atrophy (Anwar et al, 2018(Anwar et al, , 2019a(Anwar et al, , 2019b, an increase in the expression of IL-1ß, IL-6, and TNF-α within the brain was reported (Anwar et al, 2018(Anwar et al, , 2019a(Anwar et al, , 2019b (Figure 3). Subsequent activation of NF-κB, MAPK activation, and PI3K/Akt was directly observed following the release of these pro-inflammatory factors associated with a disruption in microglial M1-M2 hemostasis with a complete shift towards M1 production ending with the deposition of AD hallmarks in brain tissues on long-term diseases (Anwar, 2019;Anwar et al, 2018Anwar et al, , 2019aAnwar et al, , 2019bMehta et al, 2013).…”