First of all, stop using the term, neuroprotection! Neuronal cascade of death is the correct term! It gives absolutely NO SENSE OF URGENCY! If you tell your patients, you know nothing about stopping the 5 causes of the neuronal cascade of death in the first week thus letting die hundreds of millions to billions of neurons. They might just get angry with your incompetence!
Send me hate mail on this: oc1dean@gmail.com. I'll print your complete statement with your name and my response in my blog. Or are you afraid to engage with my stroke-addled mind? I would like to know why you aren't solving stroke to 100% recovery, because this doesn't solve stroke recovery at all!
Evaluating the Effectiveness of Neuroprotective Strategies in Enhancing Post-stroke Recovery: A Systematic Review of Meta-Analyses and Clinical Trials
DOI: 10.7759/cureus.71343
Cite this article as: Hassan B, Dabas M M, Kanemitsu K, et al. (October 12, 2024) Evaluating the Effectiveness of Neuroprotective Strategies in Enhancing Post-stroke Recovery: A Systematic Review of Meta-Analyses and Clinical Trials. Cureus 16(10): e71343. doi:10.7759/cureus.71343
Abstract
This systematic review evaluates the effectiveness of various neuroprotective strategies in enhancing recovery following acute ischemic stroke, focusing on interventions such as normobaric oxygen (NBO), lithium, selective serotonin reuptake inhibitors (SSRIs), and Cerebrolysin. Drawing upon data from six primary studies, including randomized controlled trials (RCTs) and meta-analyses, we assessed these therapies' impact on functional outcomes, motor recovery, and neurological improvement. Normobaric oxygen, across 12 RCTs, demonstrated limited efficacy in improving recovery outcomes or reducing mortality. Lithium, supported by animal models but with inconclusive human data, showed potential in reducing stroke volume but did not significantly enhance functional recovery in clinical trials. SSRIs, particularly fluoxetine, showed moderate success in improving motor recovery, as evidenced by the FLAME (Fluoxetine for Motor Recovery after Acute Ischaemic Stroke) trial and meta-analyses. Cerebrolysin demonstrated consistent improvement in early neurological function and motor recovery, with a number-needed-to-treat (NNT) of 7.1 for early NIHSS (National Institutes of Health Stroke Scale) score improvements. Our Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided search covered PubMed, Medline, Embase, and the Cochrane Library up to September 2024. These findings emphasize the mixed efficacy of these neuroprotective interventions and underscore the necessity for personalized treatment protocols and further large-scale, controlled trials to clarify their roles in clinical practice. This review contributes to the ongoing dialogue on optimizing post-stroke recovery and highlights the critical need for evidence-based neuroprotective strategies.
Introduction & Background
Stroke remains one of the leading causes of death and disability worldwide, with ischemic stroke accounting for the majority of cases. The pathophysiology of stroke involves a cascade of events, including excitotoxicity, oxidative stress, inflammation, and apoptosis, all contributing to brain injury and long-term neurological deficits [1]. Early intervention with neuroprotective therapies has the potential to limit such damage and enhance functional recovery [2]. Despite significant advancements in acute stroke care, such as thrombolysis and thrombectomy, there is still an unmet need for effective neuroprotective strategies that can be implemented during the subacute phase of stroke recovery [3].
We selected normobaric oxygen (NBO), lithium, selective serotonin reuptake inhibitors (SSRIs), and Cerebrolysin for review due to their unique mechanisms of action and their emerging roles in neuroprotection and post-stroke recovery. These therapies have shown varying degrees of promise in both preclinical studies and early-phase clinical trials. NBO has been explored for its ability to increase oxygen delivery to ischemic brain tissue, though meta-analyses suggest that it may not significantly improve functional outcomes [4,5]. Lithium, widely known for its mood-stabilizing effects, has demonstrated potential in reducing stroke volume and improving post-stroke function in animal models, but human data remain inconclusive. SSRIs, particularly fluoxetine, have garnered attention for their ability to enhance motor recovery post-stroke, independent of their antidepressant effects, as supported by the FLAME (Fluoxetine for Motor Recovery After Acute Ischemic Stroke) trial and subsequent meta-analyses [6]. Cerebrolysin, a neuropeptide preparation, has been the subject of multiple randomized controlled trials (RCTs) and meta-analyses, with studies suggesting its potential for early neurological improvement, though evidence of long-term benefits remains limited [7].
These four interventions were selected based on their clinical relevance, availability of substantial data from RCTs and meta-analyses, and their distinct neuroprotective mechanisms. Compared to other emerging interventions, such as hypothermia, neurotrophic factors, and stem cell therapies, NBO, lithium, SSRIs, and Cerebrolysin have garnered the most clinical attention and research, making them well-suited for a focused systematic review. The objective of this review is to evaluate the efficacy of these neuroprotective strategies in improving post-stroke recovery, particularly in terms of functional outcomes, motor recovery, and neurological improvement. By synthesizing data from clinical trials and meta-analyses, this review aims to provide a clearer understanding of the benefits and limitations of these therapies in stroke rehabilitation.
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