Protective effect of melatonin against head trauma-induced hippocampal damage and spatial memory deficits in immature rats

Özdemir, Durgül; Tugyan, Kazim; Uysal, Nazan; Sonmez, Ulker; Sönmez, Ataç; Açıkgöz, Osman; Özdemir, Nail; Duman, Murat; Özkan, Hasan

doi:10.1016/j.neulet.2005.05.055

Cited by 69 publications

(64 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…108 -111 Unfortunately, only one of these promising compounds, melatonin, has been tested in a model of TBI in the immature brain, where it attenuates hippocampal neuronal cell death and improves spatial memory function. 105 Human studies. Despite such compelling experimental evidence, clinical trials using antioxidants in TBI have been less successful.…”

Section: Oxidative Damagementioning

confidence: 99%

Traumatic injury to the immature brain: Inflammation, oxidative injury, and iron-mediated damage as potential therapeutic targets

Potts

Koh

Whetstone

et al. 2006

NeuroRX

137

View full text Add to dashboard Cite

Summary: Traumatic brain injury (TBI) is the leading cause of morbidity and mortality among children and both clinical and experimental data reveal that the immature brain is unique in its response and vulnerability to TBI compared to the adult brain. Current therapies for pediatric TBI focus on physiologic derangements and are based primarily on adult data. However, it is now evident that secondary biochemical perturbations play an important role in the pathobiology of pediatric TBI and may provide specific therapeutic targets for the treatment of the head-injured child. In this review, we discuss three specific components of the secondary pathogenesis of pediatric TBIinflammation, oxidative injury, and iron-induced damage -and potential therapeutic strategies associated with each. The inflammatory response in the immature brain is more robust than in the adult and characterized by greater disruption of the blood-brain barrier and elaboration of cytokines. The immature brain also has a muted response to oxidative stress compared to the adult due to inadequate expression of certain antioxidant molecules. In addition, the developing brain is less able to detoxify free iron after TBI-induced hemorrhage and cell death. These processes thus provide potential therapeutic targets that may be tailored to pediatric TBI, including anti-inflammatory agents such as minocycline, antioxidants such as glutathione peroxidase, and the iron chelator deferoxamine.

show abstract

Section: Oxidative Damagementioning

confidence: 99%

Traumatic injury to the immature brain: Inflammation, oxidative injury, and iron-mediated damage as potential therapeutic targets

Potts

Koh

Whetstone

et al. 2006

NeuroRX

137

View full text Add to dashboard Cite

show abstract

“…It is well known that hippocampus-related learning and memory are affected with head trauma (38). In our previous studies, we demonstrated that learning and memory were impaired with head trauma in immature rats (31). Several previous studies have shown that traumatic insult causes neuronal injury in the hippocampus (31,38).…”

Section: A B C Dmentioning

confidence: 64%

“…Children have a higher survival rates compared to adults with head trauma; but, the long-term sequelae are often more devastating in children depending on the age and developmental period (1). The cognitive dysfunction is a common sequela of head trauma, which is not limited to severe injury but it can be seen in mild and moderate injury (4,17,31,32).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Uysal¹,

Baykara²,

Kıray³

et al. 2012

Turkish Neurosurgery

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Although injury-induced cell death disrupts the circuit initially, our data call into question a causal relationship between protection of the CA3 neurons and postinjury performance in the MWM. Several groups have reported a treatment-related improvement in learning and/or memory after experimental TBI in conjunction with CA3 neuronal survival (Sanderson et al, 1999, Leoni et al, 2000, Kline et al, 2001, Philips et al, 2001, Floyd et al, 2002, Kline et al, 2002, Ozdemir et al, 2005, Statler et al, 2006. However, other reports have clearly documented learning deficits in brain-injured animals in the absence of discernable hippocampal damage (Lyeth et al, 1990) or the converse, an improvement in MWM performance after injury without CA3 neuroprotection (Dixon et al, 2003, Hoover et al, 2004.…”

Section: Discussionmentioning

confidence: 99%

Neurotrophin-mediated neuroprotection of hippocampal neurons following traumatic brain injury is not associated with acute recovery of hippocampal function

et al. 2007

View full text Add to dashboard Cite

Traumatic brain injury (TBI) causes selective hippocampal cell death which is believed to be associated with the cognitive impairment observed in both clinical and experimental settings. The endogenous neurotrophin NT-4/5, a TrkB ligand, has been shown to be neuroprotective for vulnerable CA3 pyramidal neurons after experimental brain injury. In this study, infusion of recombinant NT-4/5 increased survival of CA2/3 pyramidal neurons to 71% after lateral fluid percussion injury in rats, compared to 55% in vehicle-treated controls. The functional outcome of this NT-4/5-mediated neuroprotection was examined using three hippocampal-dependent behavioral tests. Injury-induced impairment was evident in all three tests, but interestingly, there was no treatment-related improvement in any of these measures. Similarly, injury-induced decreased excitability in the Schaffer collaterals was not affected by NT-4/5 treatment. We propose that a deeper understanding of the factors that link neuronal survival to recovery of function will be important for future studies of potentially therapeutic agents.

show abstract

Protective effect of melatonin against head trauma-induced hippocampal damage and spatial memory deficits in immature rats

Cited by 69 publications

References 32 publications

Traumatic injury to the immature brain: Inflammation, oxidative injury, and iron-mediated damage as potential therapeutic targets

Traumatic injury to the immature brain: Inflammation, oxidative injury, and iron-mediated damage as potential therapeutic targets

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

Neurotrophin-mediated neuroprotection of hippocampal neurons following traumatic brain injury is not associated with acute recovery of hippocampal function

Contact Info

Product

Resources

About