Neuroprotective effects of progesterone in acute brain trauma and its physiological mechanism

Moscote-Salazar, Luís Rafael; Narvaez‐Rojas, Alexis Rafael; Agrawal, Amit; Satyarthee, Guru Dutta; Hoz, Shmaryahu; Maraby-Salgado, Johana; Joaquim, Andrei Fernandes

doi:10.4103/2221-6189.228874

Cited by 2 publications

(2 citation statements)

References 4 publications

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“…We contemplated various aspects of NOS like the ability to cross BBB; antagonism of bradykinin receptors; effect of bradykinin antagonism, ultimately reduced in ammation, on ischemia; high safety pro le; its cytoprotective activity; ease of administration and inexpensive use for the treatment of other pathological conditions (Souza et al 2003;Landen et al 2004). Moreover, PG and NOS have been reported for their bene cial effect on the ischemic injury but both agents exhibited different mechanisms to reduce brain damage (Mahmoudian et al 2003;Mahmoudian et al 2015;Moscote -Salazar et al 2018;Guennoun 2019).…”

Section: Introductionmentioning

confidence: 99%

“…We also determined vital pharmacokinetic parameters in the brain and plasma to substantiate the pharmacological actions of the co-administration of both agents. Progesterone (PG), a neurosteroid, exhibits neuroprotection effects by modulating the transcription of target genes by interacting with intracellular progesterone receptors (PR) and neural PR (Gruenbaum et al 2016; Gaignard et al 2017;Zhu et al 2017;Moscote-Salazar et al 2018;Guennoun et al 2019). PG promotes regeneration of central myelin and regulates in ammation by microglia stabilization (Ghoumari et al 2005;El-Etr et al 2015).…”

Section: Introductionmentioning

confidence: 99%

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Combination Therapy for Cerebral Ischemia: Do Progesterone and Noscapine Provide Better Neuroprotection Than Either Alone in the Treatment ?

Kawadkar¹,

Mandloi²,

Singh³

et al. 2021

Preprint

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Purpose: Ischemic stroke presents multifaceted pathological outcomes with overlapping mechanisms of cerebral injury. High mortality and disability with stroke warrant a novel multi-targeted therapeutic approach. The neuroprotection with progesterone (PG) and noscapine (NOS) on cerebral ischemia-reperfusion (I-R) injury was demonstrated individually, but the outcome of combination treatment to alleviate cerebral damage is still unexplored.Methods: Randomly divided groups of rats (n=6) were Sham-operated, I-R, PG (8mg/kg), NOS (10mg/kg), and PG+NOS (8mg/kg+10mg/kg). The rats exposed to bilateral common carotid artery occlusion, except Sham-operated to investigate the therapeutic outcome of PG and NOS alone and in combination on I-R injury. Besides the alterations in cognitive and motor abilities, we estimated infarct area, oxidative stress, blood-brain barrier (BBB) permeability, and histology after treatment. Pharmacokinetic parameters like Cmax, Tmax, half-life, and AUC0-t were estimated in biological samples to substantiate the therapeutic outcomes of the combination treatment.Results: We report PG and NOS prevent loss of motor ability and improved spatial memory after cerebral I-R injury. Combination treatment significantly reduced inflammation and restricted infarction; it attenuated oxidative stress, BBB damage, and improved grip strength. Histopathological analysis demonstrated a significant reduction in leukocyte infiltration with the most profound effect in the combination group. Simultaneous analysis of PG and NOS in plasma revealed enhanced peak drug concentration, improved AUC, and prolonged half-life; the drug levels in the brain have increased significantly for both. Conclusion: We conclude that PG and NOS have beneficial effects against brain damage and, the co-administration further reinforced neuroprotection in the cerebral ischemia-reperfusion injury.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Combination Therapy for Cerebral Ischemia: Do Progesterone and Noscapine Provide Better Neuroprotection Than Either Alone in the Treatment ?

Kawadkar¹,

Mandloi²,

Singh³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

RETRACTED ARTICLE: Combination therapy for cerebral ischemia: do progesterone and noscapine provide better neuroprotection than either alone in the treatment?

Kawadkar

Mandloi

Singh

et al. 2022

Naunyn-Schmiedeberg's Arch Pharmacol

View full text Add to dashboard Cite

Purpose: Ischemic stroke presents multifaceted pathological outcomes with overlapping mechanisms of cerebral injury. High mortality and disability with stroke warrant a novel multi-targeted therapeutic approach. The neuroprotection with progesterone (PG) and noscapine (NOS) on cerebral ischemiareperfusion (I-R) injury was demonstrated individually, but the outcome of combination treatment to alleviate cerebral damage is still unexplored.Methods: Randomly divided groups of rats (n=6) were Sham-operated, I-R, PG (8mg/kg), NOS (10mg/kg), and PG+NOS (8mg/kg+10mg/kg). The rats exposed to bilateral common carotid artery occlusion, except Sham-operated to investigate the therapeutic outcome of PG and NOS alone and in combination on I-R injury. Besides the alterations in cognitive and motor abilities, we estimated infarct area, oxidative stress, blood-brain barrier (BBB) permeability, and histology after treatment. Pharmacokinetic parameters like Cmax, Tmax, half-life, and AUC 0-t were estimated in biological samples to substantiate the therapeutic outcomes of the combination treatment.Results: We report PG and NOS prevent loss of motor ability and improved spatial memory after cerebral I-R injury. Combination treatment signi cantly reduced in ammation and restricted infarction; it attenuated oxidative stress, BBB damage, and improved grip strength. Histopathological analysis demonstrated a signi cant reduction in leukocyte in ltration with the most profound effect in the combination group. Simultaneous analysis of PG and NOS in plasma revealed enhanced peak drug concentration, improved AUC, and prolonged half-life; the drug levels in the brain have increased signi cantly for both. Conclusion:We conclude that PG and NOS have bene cial effects against brain damage and, the coadministration further reinforced neuroprotection in the cerebral ischemia-reperfusion injury.

show abstract

Neuroprotective effects of progesterone in acute brain trauma and its physiological mechanism

Cited by 2 publications

References 4 publications

Combination Therapy for Cerebral Ischemia: Do Progesterone and Noscapine Provide Better Neuroprotection Than Either Alone in the Treatment ?

Combination Therapy for Cerebral Ischemia: Do Progesterone and Noscapine Provide Better Neuroprotection Than Either Alone in the Treatment ?

RETRACTED ARTICLE: Combination therapy for cerebral ischemia: do progesterone and noscapine provide better neuroprotection than either alone in the treatment?

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