Plasma levels of BDNF and EGF are reduced in acute stroke patients

Øverberg, Linda Thøring; Lugg, Elise Fritsch; Gaarder, Mona; Langhammer, Birgitta; Thommessen, Bente; Rønning, Ole Morten; Morland, Cecilie

doi:10.1016/j.heliyon.2022.e09661

Cited by 7 publications

(8 citation statements)

References 65 publications

(70 reference statements)

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“…In conclusion, EGF+GHRP6-based therapy is biologically plausible as a therapeutic intervention, given that both serum levels of EGF and insulin-like growth factor-1 (IGF-1) (as the main effect induced by GHRP6) were substantially lower in stroke patients and are determinant factors of ischemic stroke outcomes ( 76 , 77 ). Thus, this combined therapy could also be considered as a replacement therapy.…”

Section: Discussionmentioning

confidence: 99%

Combination therapy of Epidermal Growth Factor and Growth Hormone-Releasing Hexapeptide in acute ischemic stroke: a phase I/II non-blinded, randomized clinical trial

Hernández-Bernal,

Estenoz-García,

Gutiérrez-Ronquillo

et al. 2024

Front. Neurol.

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ObjectiveThis study tested the hypothesis that a neuroprotective combined therapy based on epidermal growth factor (EGF) and growth hormone-releasing hexapeptide (GHRP6) could be safe for acute ischemic stroke patients, admitting up to 30% of serious adverse events (SAE) with proven causality.MethodsA multi-centric, randomized, open-label, controlled, phase I-II clinical trial with parallel groups was conducted (July 2017 to January 2018). Patients aged 18–80 years with a computed tomography-confirmed ischemic stroke and less than 12 h from the onset of symptoms were randomly assigned to the study groups I (75 μg rEGF + 3.5 mg GHRP6 i.v., n=10), II (75 μg rEGF + 5 mg GHRP6 i.v., n=10), or III (standard care control, n=16). Combined therapy was given BID for 7 days. The primary endpoint was safety over 6 months. Secondary endpoints included neurological (NIHSS) and functional [Barthel index and modified Rankin scale (mRS)] outcomes.ResultsThe study population had a mean age of 66 ± 11 years, with 21 men (58.3%), a baseline median NIHSS score of 9 (95% CI: 8–11), and a mean time to treatment of 7.3 ± 2.8 h. Analyses were conducted on an intention-to-treat basis. SAEs were reported in 9 of 16 (56.2%) patients in the control group, 3 of 10 (30%) patients in Group I (odds ratio (OR): 0.33; 95% CI: 0.06–1.78), and 2 of 10 (20%) patients in Group II (OR: 0.19; 95% CI: 0.03–1.22); only two events in one patient in Group I were attributed to the intervention treatment. Compliance with the study hypothesis was greater than 0.90 in each group. Patients treated with EGF + GHRP6 had a favorable neurological and functional evolution at both 90 and 180 days, as evidenced by the inferential analysis of NIHSS, Barthel, and mRS and by their moderate to strong effect size. At 6 months, proportion analysis evidenced a higher survival rate for patients treated with the combined therapy. Ancillary analysis including merged treated groups and utility-weighted mRS also showed a benefit of this combined therapy.ConclusionEGF + GHRP6 therapy was safe. The functional benefits of treatment in this study supported a Phase III study.Clinical Trial RegistrationRPCEC00000214 of the Cuban Public Registry of Clinical Trials, Unique identifier: IG/CIGB-845I/IC/1601.

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Section: Discussionmentioning

confidence: 99%

Combination therapy of Epidermal Growth Factor and Growth Hormone-Releasing Hexapeptide in acute ischemic stroke: a phase I/II non-blinded, randomized clinical trial

Hernández-Bernal,

Estenoz-García,

Gutiérrez-Ronquillo

et al. 2024

Front. Neurol.

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“…Although stroke is known to lead to cognitive decline, we cannot say with certainty that the increased proportion of cognitive impairment in stroke patients compared to controls was solely due to stroke, as it is not possible to rule out prestroke cognitive impairment. Some authors report that 10% of stroke patients had prestroke dementia [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Serum Level of Brain-Derived Neurotrophic Factor and Thrombotic Type Are Predictive of Cognitive Impairment in the Acute Period of Ischemic Strokes Patients

Havlovska¹,

Lytvynenko²,

Shkodina³

2023

Neurology Research International

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40–70% of patients after a stroke, including a mild one, may experience cognitive impairment. Brain-derived neurotrophic factor (BDNF) plays a significant role in the pathogenesis and rehabilitation of ischemic stroke and also affects the patients’ recovery prognosis. An association between cognitive impairment in the poststroke period and lower peripheral BDNF levels is known, but the prognostic significance of serum BDNF levels and clinical characteristics for the risk of developing cognitive impairment in the acute period remains uncertain. We conducted a prospective cohort study of patients in the acute phase of ischemic stroke. Clinical examination, assessment of neurological status, neuropsychological testing, and laboratory analyzes were performed on patients at 1 and 14 days after ischemic stroke. The state of cognitive functions was assessed by the Mini-Mental State Examination scale. Quantification of BDNF in blood serum was performed by solid-phaseenzyme-linked immunosorbent assay (ELISA). We found that within 14 days after an acute ischemic stroke, we found a decrease in the clinical severity of patients compared to 1 day of the onset of the disease before the start of treatment and a significant decrease in the level of BDNF in the blood serum of patients with ischemic stroke both on the first and on the 14th day. However, during the 2 weeks of the acute period, no significant changes were detected, despite the general improvement of the clinical condition. In our study, cognitive impairment was found in almost half of the patients on the first day of ischemic stroke, and there was no significant reduction in this prevalence over 2 weeks. We found that a low level of BDNF and a thrombotic subtype of ischemic stroke can be risk factors for cognitive impairment in the acute period, which can be useful in planning treatment and rehabilitation measures.

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“…Administration of exogenous EGF to mice with middle cerebral artery occlusion model could alleviate the neurological deficit and reduce infarct volume; In addition, EGF is also an effective mitogen, which can stimulate neural progenitor cells in the subventricular zone, and thus promote neurogenesis 31 . Notably, in AIS patients, the levels of EGF in plasma were lower than that in the healthy subjects 32 . Therefore, increasing EGF levels after stroke may be beneficial for recovery.…”

Section: Discussionmentioning

confidence: 99%

“…31 Notably, in AIS patients, the levels of EGF in plasma were lower than that in the healthy subjects. 32 Therefore, increasing EGF levels after stroke may be beneficial for recovery. We found that repeated application of RIC after AIS elevated EGF level in serum, suggesting that RIC played a protective role in AIS partly due to increasing endogenous EGF.…”

Section: Discussionmentioning

confidence: 99%

Remote Ischemic Conditioning for Motor Recovery after Acute Ischemic Stroke

Ren

et al. 2023

The Neurologist

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Background: Remote ischemic conditioning (RIC) has shown an impressive neuroprotective effect on acute ischemic stroke (AIS) in animal experiments. But whether chronic RIC improves long-term functional outcomes remains unclear. Materials and Methods:We performed a non-randomized controlled trial. Eligible patients (aged 18 -80 y) with hemiplegia caused by AIS were allocated to the RIC group and the control group. All participants received normal protocol rehabilitation therapy. Patients in the RIC group underwent RIC twice daily for 90 days. The outcome included the 90-day Fugl-Meyer Assessment (FMA) scores and modified Rankin's scale (mRS) scores, as well as changes in angiogenesis-related factors in serum from baseline to 90 days.Results: Twenty-seven patients were included in the analysis (13 in the RIC group and 14 in the control group). There was no significant difference in 90-day total FMA scores between the two groups. Lower limb FMA scores at day 90 were significantly higher in the RIC group (32.8 8.7 vs. 24.8 5.4, adjusted P = 0.042). The proportion of favorable outcome (mRS < 2) was higher in the RIC group than that in the control group, but no significant difference was detected (8 [61.5%] vs. 7 [50%], P = 0.705). A significant increase has been found in the level of epidermal growth factor (EGF) in serum (9.4 [1.1 to 25.7] vs. −8.7 [−15.1 to 4.7], P = 0.036) after chronic RIC procedure. Conclusion:This study investigated the role that RIC plays in AIS recovery, especially in motor function. RIC may have beneficial effects on lower limbs recovery by enhancing the EGF level. The effect of RIC on motor recovery should be further validated in future studies.

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Plasma levels of BDNF and EGF are reduced in acute stroke patients

Cited by 7 publications

References 65 publications

Combination therapy of Epidermal Growth Factor and Growth Hormone-Releasing Hexapeptide in acute ischemic stroke: a phase I/II non-blinded, randomized clinical trial

Combination therapy of Epidermal Growth Factor and Growth Hormone-Releasing Hexapeptide in acute ischemic stroke: a phase I/II non-blinded, randomized clinical trial

Serum Level of Brain-Derived Neurotrophic Factor and Thrombotic Type Are Predictive of Cognitive Impairment in the Acute Period of Ischemic Strokes Patients

Remote Ischemic Conditioning for Motor Recovery after Acute Ischemic Stroke

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