Recovering from a stroke can feel like climbing a mountain. But what if I told you there's a base camp, a midpoint, and a peak in your journey to recovery, each with its own set of tools and strategies to help you reach the summit? This guide is your map to that mountain, offering a detailed exploration of how peptides, lifestyle adjustments, and neuroprotective strategies can not only aid in recovery but also protect and enhance your brain's health post-stroke.
Phase 1: Repair - 6 Weeks
In the aftermath of a stroke, the brain is like a city after an earthquake. The priority is to clear the debris and start the rebuilding process. Here's how:
CJC-1295 + Ipamorelin
Administer 100mcg of each, before bed, three times a week.
BPC-157 + TB-500
Inject 250-500mcg of BPC-157/TB-500 daily
GHK-Cu
At a dose of 1-2mg daily
Phase 2: Protection - 30 Days
Once the repairs are underway, it's time to fortify the defenses, preparing the brain to withstand future assaults. These peptides serve as your brain's personal bodyguards, offering neuroprotection, stress resilience, and cognitive enhancement. They ensure the brain's functions are supported and safeguarded.
Semax
500mcg-1000mcg of Semax subcutaneously, depending on the subjects' responsiveness, daily for up to 30 days.
Selank
The proposed dosage for subcutaneous injections ranges from 150mcg to 300mcg once per day, once again for up to 30 days.
Phase 3: Regrowth - 21 Days
With the groundwork laid and defenses up, now we aim for growth, expanding beyond the pre-stroke capacities.
Cerebrolysin
For stroke specifically, a dosage of 10-20 ml for 21 days is suggested.
The Path Forward
Embarking on this journey requires more than just following a regimen. It demands a holistic commitment to lifestyle changes, physical rehabilitation, and mental health support. The road to recovery is indeed steep, but with each step, you move closer to reclaiming your health and vitality.
Remember, every journey begins with a single step. And in the journey of stroke recovery, these peptide therapies are your stepping stones to a stronger, healthier brain.
Let's embark on this path together, with eyes on the horizon and hope as our guide.
References:
Motor impairment is the most common and widely recognised clinical outcome after stroke. Current clinical practice in stroke rehabilitation focuses mainly on physical therapy, with no pharmacological intervention approved to facilitate functional recovery. Several studies have documented positive effects of growth hormone (GH) on cognitive function after stroke, but surprisingly, the effects on motor function remain unclear. In this study, photothrombotic occlusion targeting the motor and sensory cortex was induced in adult male mice. Two days post-stroke, mice were administered with recombinant human GH or saline, continuing for 28 days, followed by evaluation of motor function. Three days after initiation of the treatment, bromodeoxyuridine was administered for subsequent assessment of cell proliferation. Known neurorestorative processes within the peri-infarct area were evaluated by histological and biochemical analyses at 30 days post-stroke. This study demonstrated that GH treatment improves motor function after stroke by 50%–60%, as assessed using the cylinder and grid walk tests. Furthermore, the observed functional improvements occurred in parallel with a reduction in brain tissue loss, as well as increased cell proliferation, neurogenesis, increased synaptic plasticity and angiogenesis within the peri-infarct area. These findings provide new evidence about the potential therapeutic effects of GH in stroke recovery.
Sonia Sanchez-Bezanilla,1,2 N. David Åberg,3,4 Patricia Crock,2,5 Frederick R. Walker,1,2,6,7 Michael Nilsson,1,2,6,7,8 Jörgen Isgaard,1,3,4,*† and Lin Kooi Ong1,2,6,9,*†
Published online 2020 Jan 17
Traumatic brain injury (TBI) is a major public health issue, and yet medical science has little to offer for the persistent symptoms that prevent many of these individuals from fully re-entering society. Post-traumatic hypopituitarism, and specifically growth hormone deficiency (GHD), has been found in a large percentage of individuals with chronic moderate to severe TBI. Presently, there are no published treatment studies of hormone replacement in this population. In this study, 83 subjects with chronic TBI were screened for hypopituitarism. Forty-two subjects were found to have either GHD or GH insufficiency (GHI), of which 23 agreed to be randomized to either a year of GH replacement or placebo. All subjects completed the study with no untoward side effects from treatment. A battery of neuropsychological tests and functional measures were administered before and after treatment. Improvement was seen on the following tests: Dominant Hand Finger Tapping Test, Wechsler Adult Intelligence Scale III–Information Processing Speed Index, California Verbal Learning Test II, and the Wisconsin Card Sorting Test (executive functioning). The findings of this pilot study provide preliminary evidence suggesting that some of the cognitive impairments observed in persons who are GHD/GHI after TBI may be partially reversible with appropriate GH replacement therapy.
Walter M. High, Jr.,corresponding author1,,2,,3,,4 Maria Briones-Galang,5 Jessica A. Clark,1,,3 Charles Gilkison,6 Kurt A. Mossberg,7 Dennis J. Zgaljardic,8,,9 Brent E. Masel,9 and Randall J. Urban6
2010 Sep
We reviewed the pleiotropic beneficial effects of the stable gastric pentadecapeptide BPC 157, three very recent demonstrations that may be essential in the gut-brain and brain-gut axis operation, and therapy application in the central nervous system disorders, in particular. Firstly, given in the reperfusion, BPC 157 counteracted bilateral clamping of the common carotid arteries-induced stroke, sustained brain neuronal damages were resolved in rats as well as disturbed memory, locomotion, and coordination. This therapy effect supports particular gene expression in hippocampal tissues that appeared in BPC 157-treated rats. Secondly, there are L-NG-nitro arginine methyl ester (L-NAME)- and haloperidol-induced catalepsy as well as the rat acute and chronic models of ‘positive-like’ schizophrenia symptoms, that BPC 157 counteracted, and resolved the complex relationship of the nitric oxide-system with amphetamine and apomorphine (dopamine agents application), MK-801 (non-competitive antagonist of the N-methyl-D-aspartate receptor) and chronic methamphetamine administration (to induce sensitivity). Thirdly, after rat spinal cord compression, there were advanced healing and functional recovery (counteracted tail paralysis). Likewise, in BPC 157 therapy, there is specific support for each of these topics: counteracted encephalopathies; alleviated vascular occlusion disturbances (stroke); counteracted dopamine disturbances (dopamine receptors blockade, receptors super sensitivity development, or receptor activation, over-release, nigrostriatal damage, vesicles depletion), and nitric oxide-system disturbances (“L-NAME non-responsive, L-arginine responsive,” and “L-NAME responsive, L-arginine responsive”) (schizophrenia therapy); inflammation reduction, nerve recovery in addition to alleviated hemostasis and vessels function after compression (spinal cord injury therapy). Thus, these disturbances may be all resolved within the same agent’s beneficial activity, i.e., the stable gastric pentadecapeptide BPC 157.
Jakša Vukojević, MD, PhD,1,* Marija Milavić,2 Darko Perović,1 Spomenko Ilić,1 Andrea Zemba Čilić,3 Nataša Đuran,4 Sanja Štrbe,3 Zoran Zoričić,5 Igor Filipčić,6 Petrana Brečić,4 Sven Seiverth,2 and Predrag Sikirić1
2022 Mar
Gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, an anti-ulcer peptide, efficient in inflammatory bowel disease trials (PL 14736), no toxicity reported, improved muscle crush injury. After an induced traumatic brain injury (TBI) in mice by a falling weight, BPC 157 regimens (10.0 µg, 10.0 ng/kg i.p.) demonstrated a marked attenuation of damage with an improved early outcome and a minimal postponed mortality throughout a 24 h post-injury period. Ultimately, the traumatic lesions (subarachnoidal and intraventricular haemorrhage, brain laceration, haemorrhagic laceration) were less intense and consecutive brain edema had considerably improved. Given prophylactically (30 min before TBI) the improved conscious/unconscious/death ratio in TBI-mice was after force impulses of 0.068 N s, 0.093 N s, 0.113 N s, 0.130 N s, 0.145 N s, and 0.159 N s. Counteraction (with a reduction of unconsciousness, lower mortality) with both µg- and ng-regimens included the force impulses of 0.068–0.145 N s. A higher regimen presented effectiveness also against the maximal force impulse (0.159 N s). Furthermore, BPC 157 application immediately prior to injury was beneficial in mice subjected to force impulses of 0.093 N s-TBI. For a more severe force impulse (0.130 N s, 0.145 N s, or 0159 N s), the time-relation to improve the conscious/unconscious/death ratio was: 5 min (0.130 N s-TBI), 20 min (0.145 N s-TBI) or 30 min (0.159 N s-TBI).
Mario Tudor, Ivan Jandric, Anton Marovic, Miroslav Gjurasin, Darko Perovic, Bozo Radic, Alenka Boban Blagaic, Danijela Kolenc, Luka Brcic, Kamelija Zarkovic, Sven Seiwerth, Predrag Sikiric
February 2010
Neuroprotective and neurorestorative effects of Thymosin beta 4 treatment following experimental traumatic brain injury Traumatic brain injury (TBI) remains a leading cause of mortality and morbidity worldwide. No effective pharmacological treatments are available for TBI because all Phase II/III TBI clinical trials have failed. This highlights a compelling need to develop effective treatments for TBI. Endogenous neurorestoration occurs in the brain after TBI, including angiogenesis, neurogenesis, synaptogenesis, oligodendrogenesis and axonal remodeling, which may be associated with spontaneous functional recovery after TBI. However, the endogenous neurorestoration following TBI is limited. Treatments amplifying these neurorestorative processes may promote functional recovery after TBI. Thymosin beta4 (Tβ4) is the major G-actin-sequestering molecule in eukaryotic cells. In addition, Tβ4 has other properties including anti-apoptosis and anti-inflammation, promotion of angiogenesis, wound healing, stem/progenitor cell differentiation, and cell migration and survival, which provide the scientific foundation for the corneal, dermal, and cardiac wound repair multicenter clinical trials. Here, we describe Tβ4 as a neuroprotective and neurorestorative candidate for treatment of TBI.
Ye Xiong, M.D., Ph.D.,1 Asim Mahmood, M.D.,1 Yuling Meng, Ph.D.,1 Yanlu Zhang, M.D.,1 Zheng Gang Zhang, M.D., Ph.D.,2 Daniel C. Morris, M.D.,3 and Michael Chopp, Ph.D.2,4
2013 Oct 1
Peripheral neuropathy is one of the most common complications of diabetes mellitus. Using a mouse model of diabetic peripheral neuropathy, we tested the hypothesis that thymosin β 4 (Tβ4) ameliorates diabetes–induced neurovascular dysfunction in the sciatic nerve and promotes recovery of neurological function from diabetic peripheral neuropathy. Tβ4 treatment of diabetic mice increased functional vascular density and regional blood flow in the sciatic nerve, and improved nerve function. Tβ4 upregulated angiopoietin-1 (Ang1) expression, but suppressed Ang2 expression in endothelial and Schwann cells in the diabetic sciatic nerve. In vitro, incubation of Human Umbilical Vein Endothelial Cells (HUVECs) with Tβ4 under high glucose condition completely abolished high glucose-downregulated Ang1 expression and high glucose-reduced capillary-like tube formation. Moreover, incubation of HUVECs under high glucose with conditioned medium collected from Human Schwann cells (HSCs) treated with Tβ4 significantly reversed high glucose-decreased capillary-like tube formation. PI3K/Akt signaling pathway is involved in Tβ4-regulated Ang1 expression on endothelial and Schwann cells. These data indicate that Tβ4 likely acts on endothelial cells and Schwann cells to preserve and/or restore vascular function in the sciatic nerve which facilitates improvement of peripheral nerve function under diabetic neuropathy. Thus, Tβ4 has potential for the treatment of diabetic peripheral neuropathy.
Lei Wang,1 Michael Chopp,1,2 Alexandra Szalad,1 Zhongwu Liu,1 Mei Lu,1 Li Zhang,1 Jing Zhang,1 Rui Lan Zhang,1 Dan Morris,1 and Zheng Gang Zhang1
2013 Dec 1
Glycine-histidine-lysine (GHK) is a human tripeptide that enhances wound healing, exerts neuroprotective effects against neurodegenerative disease, and improves tissue regeneration. This study examined whether GHK can alleviate injury due to intracerebral hemorrhage (ICH). Briefly, adult Wistar rats in GHK pretreatment groups were injected with GHK (1 or 10 mg/kg, i.p.) every 24 h for 3 days. Water content and intact neurons were detected in the rats 3 days after ICH, and the neurological deficit scores were examined in the rats at 4, 24, 72, and 168 h after ICH. Apoptosis was evaluated via caspase-3 immunohistochemistry, Nissl staining, and TUNEL assay. We also examined the effect of GHK on the expression of related proteins in SH-SY5Y cells via Western blotting. The expression of miR-339-5p was examined via real-time polymerase chain reaction analyses. GHK improved neurological deficits, reduced water content in the brain and inhibited neuronal apoptosis in ICH rats. It also prevented the apoptosis of SH-SY5Y cells with hemin treatment. Furthermore, GHK downregulated miR-339-5p expression, and overexpression of miR-339-5p partially reversed the anti-apoptotic effects of GHK in SH-SY5Y cells. Our findings suggest that the p38 MAPK pathway is involved in the GHK-induced downregulation of miR-339-5p, and that the miR-339-5p/VEGFA axis plays a role in preventing neuronal apoptosis following ICH injury. These findings indicate that GHK may represent a novel therapeutic strategy for ICH.
Heyu Zhang, Yanzhe Wang, and Zhiyi He*
2018 Sep 20
Intracerebral hemorrhage (ICH) is a major type of cerebrovascular disease with poor prognosis. Recent studies have shown that Glycyl-l-histidyl-l-lysine (GHK) is a kind of natural human tripeptide which could inhibit inflammation and against neurodegenerative diseases, but neither its role nor the mechanisms in ICH have yet been explicit. Currently, we investigated the possible strategies of GHK on ICH injury. Neurological deficit scores, brain water content, Nissl staining, and aquaporin 4 (AQP4) immunohistochemistry were detected in different groups of rats. The expression of microRNAs (miRNAs) was examined by real-time PCR. Inflammatory factors were detected using enzyme-linked immunosorbent assay (ELISA). Cell viability and cell proliferation were detected by Cell Counting Kit-8 (CCK-8). Matrix metalloproteinase 2 (MMP2), MMP9, tissue inhibitors of metalloproteinase-1 (TIMP1), AQP4 expression were detected/assessed using western blot. We observed that 5 and 10 μg/g of GHK improved neurological recovery by significantly reducing brain water content, improving neurological deficits, and promoting neuron survival. Besides, GHK alleviated inflammatory reaction and downregulated AQP4 expression. Furthermore, the effects of GHK on astrocyte were associated with the upregulation of miRNA-146a-3p, which partially regulated the expression of AQP4. Our results demonstrated that the phosphatidylinositol 3-kinase (PI3K)/AKT pathway participated in the GHK-induced upregulation of miR-146a-3p and miR-146a-3p/AQP4 interaction plays a role in the injury following ICH. These findings suggested that GHK could provide a novel therapeutic strategy for ICH.
Heyu Zhang,1,2,3 Yanzhe Wang,3 Ling Lian,1,2 Cheng Zhang,1,2,* and Zhiyi He3,*
2020 Oct 28
To evaluate the efficacy of semax and timing of rehabilitation on the dynamics of plasma BDNF levels, motor performance, and Barthel index score in patients after ischemic stroke (IS). Material and methods: One hundred and ten patients after IS (43 men, 67 women, mean age 58.0±9.7, Ме 63 years) were examined. All patients were divided into early (89±9 days) and late (214±22 days) rehabilitation groups. Each group was subdivided into semax+ and semax- subgroups. Standard regimen of semax included 2 courses (6000 mcg/day) for 10 days with 20 day interval. Plasma BDNF levels, motor performance on the British Medical Research Council scale and Barthel index were assessed in all groups. Results: Administration of semax, regardless of the timing of rehabilitation, increased BDNF plasma levels which remained high during the whole study period. In semax- subgroups high BDNF plasma levels were positively correlated with early rehabilitation. Administration of semax and high BDNF levels accelerated the improvement and ameliorated the final outcome of Barthel score index. There was a positive correlation between BDNF plasma levels and Barthel score, as well as a correlation between early rehabilitation and motor performance improvement. The correlation between BDNF plasma levels and Barthel score was modified by the timing of rehabilitation. Conclusion: Early rehabilitation and administration of semax increase BDNF plasma level, speed functional recovery, and improve motor performance.
Zhurnal nevrologii i psikhiatrii im S S Korsakova 118(3):61
January 2018
Ischemic stroke continues to be one of the leading causes of death and disability in the adult population worldwide. The currently used pharmacological methods for the treatment of ischemic stroke are not effective enough and require the search for new tools and approaches to identify therapeutic targets and potential neuroprotectors. Today, in the development of neuroprotective drugs for the treatment of stroke, special attention is paid to peptides. Namely, peptide action is aimed at blocking the cascade of pathological processes caused by a decrease in blood flow to the brain tissues. Different groups of peptides have therapeutic potential in ischemia. Among them are small interfering peptides that block protein–protein interactions, cationic arginine-rich peptides with a combination of various neuroprotective properties, shuttle peptides that ensure the permeability of neuroprotectors through the blood–brain barrier, and synthetic peptides that mimic natural regulatory peptides and hormones. In this review, we consider the latest achievements and trends in the development of new biologically active peptides, as well as the role of transcriptomic analysis in identifying the molecular mechanisms of action of potential drugs aimed at the treatment of ischemic stroke.
Lyudmila V. Dergunova, Ivan B. Filippenkov, Svetlana A. Limborska, and Nikolay F. Myasoedov*
2023 Apr 22
The aim of this study was to examine Taftsin derivates--macrophage inhibitory factor (MIF, Thr-Lys-Pro) and heptapeptide selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) in the model of experimental intracerebral hemorrhage in rats. The double autologous blood injection in the basal nucleus was used as a model of intracerebral hemorrhage. Animals ware randomly divided into three groups--the control group (n = 5) was treated with saline, the second group (n = 5) was injected with MIF in dose 150 mkg/ kg/day, the third group (n = 5) received Selank in dose 300 mkg/kg/day. Intraperitoneal injection of peptides was used. Body weight assessment, neurological examination and brain MRI were performed in 24, 72 hours and 10 days after the hematoma formation. The effect of neuropeptides on the functional restoration in animals, in the absence of the effect on hematoma volume and perifocal edema, was found. The significant reduction of perifocal edema and hematoma volume was observed in the 10th day after the hematoma formation in all experimental groups (p < 0.05). Only the control group of animals showed the significant (p < 0.05) weight loss in the 3rd day after the operation. The rate of neurological deficit was different: the significant improvement assessed with Menzes and limb placing test scales was seen only in the groups treated with neuropeptides in the 10th day.
V I Skvortsova, T V Tvorogova, A I Dubina, D V Burenchev, L V Gubskiĭ, L V Stakhovskaia, O V Povarova
2009
Cerebrolysin and Recovery After Stroke (CARS) The nonparametric effect size on the Action Research Arm Test score on day 90 indicated a large superiority of Cerebrolysin compared with the placebo (Mann–Whitney estimator, 0.71; 95% confidence interval, 0.63–0.79; P<0.0001). The multivariate effect size on global status, as assessed using 12 different outcome scales, indicated a small-to-medium superiority of Cerebrolysin (Mann–Whitney estimator, 0.62; 95% confidence interval, 0.58–0.65; P<0.0001). The rate of premature discontinuation was <5% (3.8%). Cerebrolysin was safe and well tolerated.
Dafin F. Muresanu, Wolf-Dieter Heiss, Volker Hoemberg, Ovidiu Bajenaru, Cristian Dinu Popescu, Johannes C. Vester, Volker W. Rahlfs, Edith Doppler, Dieter Meier, Herbert Moessler and Alla Guekht
Nov 2015
Ischemic stroke continues to be one of the leading causes of death and disability in the adult population worldwide. The currently used pharmacological methods for the treatment of ischemic stroke are not effective enough and require the search for new tools and approaches to identify therapeutic targets and potential neuroprotectors. Today, in the development of neuroprotective drugs for the treatment of stroke, special attention is paid to peptides. Namely, peptide action is aimed at blocking the cascade of pathological processes caused by a decrease in blood flow to the brain tissues. Different groups of peptides have therapeutic potential in ischemia. Among them are small interfering peptides that block protein–protein interactions, cationic arginine-rich peptides with a combination of various neuroprotective properties, shuttle peptides that ensure the permeability of neuroprotectors through the blood–brain barrier, and synthetic peptides that mimic natural regulatory peptides and hormones. In this review, we consider the latest achievements and trends in the development of new biologically active peptides, as well as the role of transcriptomic analysis in identifying the molecular mechanisms of action of potential drugs aimed at the treatment of ischemic stroke.
Lyudmila V. Dergunova Ivan B. Filippenkov,Svetlana A. Limborska
Genes 2023
Senolytic treatment has potential therapeutic efficacy for acute ischemic stroke (AIS). However, the systemic treatment of senolytics may produce off-target side effects and a toxic profile, which affect analysis of the role of acute senescence of neuronal cells in pathogenesis of AIS. We constructed a novel lenti-INK-ATTAC viral vector to introduce INK-ATTAC genes to the ipsilateral brain and locally eliminate senescent brain cells by administering AP20187 to activate caspase-8 apoptotic cascade. In this study, we have found that acute senescence is triggered by middle cerebral artery occlusion (MCAO) surgery, particularly in astrocytes and cerebral endothelial cells (CECs). The upregulation of p16INK4a and senescence-associated secretory phenotype (SASP) factors including matrix metalloproteinase-3, interleukin-1 alpha and -6 were observed in oxygen-glucose deprivation-treated astrocytes and CECs. The systemic administration of a senolytic, ABT-263, prevented the impairment of brain activity from hypoxic brain injury in mice, and significantly improved the neurological severity score, rotarod performance, locomotor activity, and weight loss. The treatment of ABT-263 reduced senescence of astrocytes and CECs in MCAO mice. Furthermore, the localized removal of senescent cells in the injured brain through the stereotaxical injection of lenti-INK-ATTAC viruses generates neuroprotective effects, protecting against acute ischemic brain injury in mice. The content of SASP factors and mRNA level of p16INK4a in the brain tissue of MCAO mice were significantly reduced by the infection of lenti-INK-ATTAC viruses. These results indicate that local clearance of senescent brain cells is a potential therapy on AIS, and demonstrate the correlation between neuronal senescence and pathogenesis of AIS.
Kuan-Jung Lu,1,* Joen-Rong Sheu,1,2,* Ruei-Dun Teng,1 Tanasekar Jayakumar,5 Chi-Li Chung,3,4,6 and Cheng-Ying Hsieh2
2023 May 29
Cerebrolysin and FOXO4-DRI are a great combo.