The combined treatment with progesterone and magnesium sulfate positively affects the traumatic brain injury in immature rats.

Abstract

AIm:It is well known that head trauma results in damage in hippocampal and cortical areas of the brain and impairs cognitive functions. The aim of this study is to explore the neuroprotective effect of combination therapy with magnesium sulphate (MgSO4) and progesterone in the 7-days-old rat pups subjected to contusion injury. mAterIAl and methOds: Progesterone (8 mg/kg) and MgSO4 (150 mg/kg) were injected intraperitoneally immediately after induction of traumatic brain injury. Half of groups were evaluated 24 hours later, the remaining animals 3 weeks after trauma or sham surgery. Anxiety levels were assessed with open field activity and elevated plus maze; learning and memory performance were evaluated with Morris Water maze in postnatal 27 days.results: Combined therapy with progesterone and magnesium sulfate significantly attenuated trauma-induced neuronal death, increased brain VEGF levels and improved spatial memory deficits that appear later in life. Brain VEGF levels were higher in rats that received combined therapy compared to rats that received either medication alone. Moreover, rats that received combined therapy had reduced hipocampus and prefrontal cortex apoptosis in the acute period.COnClusIOn: These results demonstrate that combination of drugs with different mechanisms of action may be preferred in the treatment of head trauma.KeywOrds: Traumatic brain injury, Immature rat, Spatial learning and memory, Apoptosis, VEGF, Magnesium sulfate, Progesterone ÖZ AmAÇ: Kafa travmasının hipokampal ve kortikal hasar ile kognitif fonksiyonlarda bozulmaya neden olduğu bilinmektedir. Bu çalışmanın amacı, magnezyum sülfat (MgSO4) ve progesteronun combine kullanımının kontüzyon hasarı oluşturulan 7 günlük sıçan beynindeki nöroprotektif etkilerini araştırmaktır. yÖntem ve GereÇler: Travmadan hemen sonra 8 mg/kg dozunda progesteron, 150 mg/kg dozunda MgSO4 intraperitoneal tek doz olarak verildi. Deney gruplarının yarısı travmadan 24 saat sonra, kalan yarısı ise 27 günlük olduklarında değerlendirildi. Anksiyete deneyleri açık alan ve yükseltilmiş + labirent test düzenekleri kullanılarak; öğrenme ve bellek performansı ise Morris su tankı aracılığı ile 27 günlükken değerlendirildi.BulGulAr: Kombine tedavinin beyin dokusunda VEGF'yi arttırarak travma ile oluşan nöronal ölümü azalttığı ve ileriki dönemde spasyal bellek bozukluğunu iyileştirdiği görüldü. VEGF seviyesinin kombine tedavide ilaçların tek başına kullanımına göre daha fazla arttığı bulundu. Ayrıca ilaç tedavisinin akut dönemde de VEGF seviyesini arttırarak apoptozis seviyesini azalttığı görüldü. sOnuÇ: Bu sonuçlar, farklı etki mekanizmasına sahip ilaçların kombine kullanımının kafa travması tedavisinde tercih edilebileceğini göstermektedir.

Sex differences in the effect of progesterone after controlled cortical impact in adolescent mice: a preliminary study

“…Prior studies have offered contradictory results of progesterone treatment after brain injury in immature animals. 21,22 While this study was initially designed to evaluate whether or not progesterone was a safe and effective therapy for adolescent mice after CCI, we unexpectedly found gender differences in 4 week old injured mice in response to progesterone treatment. Though numerous prior studies have suggested a beneficial effect of progesterone in the setting of TBI, the vast majority of these studies have used adult males, adult ovariectomized females or reproductively senescent females.…”

Combination therapies for neurobehavioral and cognitive recovery after experimental traumatic brain injury: Is more better?

“…Thus, it is also important to identify therapies that are effective in reducing glutamate excitotoxicity in pediatrics. To this end, Uysal and colleagues (2013) evaluated the effects of a single intraperitoneal injection of magnesium sulfate (MgSO 4 ; 150 mg/kg), PROG (8 mg/kg), or their combination on cognitive outcome, cell death, neurotrophic factor expression, and hippocampal cell sparing after a weight-drop TBI in post-natal day-7 rats (no gender details indicated). Treatments were provided immediately after TBI.…”

Brain Metabolic Crisis in Traumatic Brain Injury: What Does It Mean?

“…On the other hand, LPR2 might be associated with different pathophysiological mechanisms and treatments. 4,7 In experimental TBI models, estrogen has been shown to have antioxidant effects, 12 and inhibitors of nitric oxide synthase have demonstrated to present effects on superoxide production decrease, 13 which can attenuate LPR2 metabolic crisis.…”