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Relevance:4 Technical Level:2

Page Synopsis: A medicine that could be helpful in working into the repertoire as CFS patients have preloading, volume and other circulatory issues (see Pentoxifylline


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From: Traumatic Brain Injury, Panhypopituitarism and Hormonal Evaluations as a Standard of Care


Atorvastatin used in conjunction with HRT "Statins- Dose: Atorvastatin 10 mg within 24 hours of TBI

Cerebral Blood Flow: Decrease
Thrombosis, Platelet activity, Inflammatory cytokines, Cerebral edema, microglial activity, oxidative stress, Apoptosis

Increases: Neurogenesis, Angiogenesis"

Neurorestorative Treatments for Traumatic Brain Injury

Statins, inhibitors of cholesterol biosynthesis used to lower cholesterol levels, induce angiogenesis, neurogenesis and synaptogenesis, and enhance functional recovery following TBI in rats Lu et al., 2004a; Lu et al., 2004b; Lu et al., 2007b; Wu et al., 2008b These beneficial effects of statins are independent of cholesterol-lowering action. Beneficial effects of simvastatin may be mediated through activation of Akt, Forkhead transcription factor 1 and nuclear factor–κB signaling pathways, which suppress the activation of caspase-3 and apoptotic cell death, and thereby, lead to neuronal function recovery after TBI Wu et al., 2008a


Simvastatin activates the Akt-mediated signaling pathway, subsequently upregulating the expression of growth factors and inducing neurogenesis in the dentate gyrus of the hippocampus, thereby leading to restoration of cognitive function after TBI in rats Wu et al., 2008b


In addition, simvastatin treatment provided long-lasting 3 month functional improvement following TBI in rats Mahmood et al., 2009 The protective mechanisms of statins may be partly attributed to a reduction in the inflammatory response following TBI Li et al., 2009 When administered in combination with MSCs in a rat model of TBI, atorvastatin increased MSC access and/or survival within the injured brain and enhanced functional recovery compared with either MSC or atorvastatin monotherapy Mahmood et al., 2007a, suggesting that statins might be used in conjunction with MSC transplantation for treating neurological disorders and injuries.


Given the wide use, favorable safety profile and positive clinical data for statins, the rare occurrence of serious adverse events and the extensive available preclinical data demonstrating neuroprotection and neurorestoration Wible and Laskowitz, 2010, further clinical trials are warranted to determine the neuroprotective and neurorestorative properties of statins following TBI. The effect of rosuvastatin on TBI-induced cytokine change is ongoing in a phase I/II trial, NCT00990028

ME/CFS patient Hopefulone with moderate ME/CFS greatly improved after starting atorvastatin 80 mg daily.

Interesting discussion included below,

Pathophysiology Associated with Traumatic Brain Injury: Current Treatments and Potential Novel Therapeutics
preclinical findings demonstrated that long-term atorvastatin treatment (7 months) decreased behavior and cognition, altered hippocampal biochemistry, and reduced the subcellular localization of presynaptic vesicular proteins (syntaxin, synaptophysin) (Schilling et al. 2014). More recently, the US FDA placed warning labels on statins for their potential associated cognitive side effects. Furthermore, because statins inhibit intracellular cholesterol synthesis, these compounds could indirectly disrupt formation of cholesterol-enriched plasmalemmal microdomains, cellular regions essential for neuritogenesis, and axonal growth cone guidance [described in more detail in next section (Head et al. 2013). Due to these conflicting findings, more thorough studies need to be conducted to determine whether or not acute or short-term treatment with statins after injury is an effective therapeutic strategy for alleviating complications associated with SCI and TBI in a clinical setting


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