Magnesium attenuates persistent functional deficits following diffuse traumatic brain injury in rats

Vink, Robert; O'Connor, Christine; Nimmo, Alan J.; Heath, Deanne L.

doi:10.1016/s0304-3940(02)01244-2

Cited by 76 publications

(61 citation statements)

References 19 publications

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“…42,43 Magnesium reversed persistent motor and cognitive deficits with reduction of post-traumatic stress and anxiety after brain injury in rats. 44 Magnesium therapy after TBI may not always improve the mortality and morbidity of the subjects. In patients with severe TBI, a subdural hematoma is often present, which has developed subsequent to the primary injury.…”

Section: Preclinical Studies With Magnesium In Brain Injurymentioning

confidence: 99%

Use of Magnesium in Traumatic Brain Injury

Sen¹,

Gulati

2010

Neurotherapeutics

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Summary: Depletion of magnesium is observed in animal brain and in human blood after brain injury. Treatment with magnesium attenuates the pathological and behavioral changes in rats with brain injury; however, the therapeutic effect of magnesium has not been consistently observed in humans with traumatic brain injury (TBI). Secondary brain insults are observed in patients with brain injury, which adversely affect clinical outcome. Systemic administration studies in rats have shown that magnesium enters the brain; however, inducing hypermagnesemia in humans did not concomitantly increase magnesium levels in the CSF. We hypothesize that the neuroprotective effects of magnesium in TBI patients could be observed by increasing its brain bioavailability with mannitol. Here, we review the role of magnesium in brain injury, preclinical studies in brain injury, clinical safety and efficacy studies in TBI patients, brain bioavailability studies in rat, and pharmacokinetic studies in humans with brain injury. Neurodegeneration after brain injury involves multiple biochemical pathways. Treatment with a single agent has often resulted in poor efficacy at a safe dose or toxicity at a therapeutic dose. A successful neuroprotective therapy needs to be aimed at homeostatic control of these pathways with multiple agents. Other pharmacological agents, such as dexanabinol and progesterone, and physiological interventions, with hypothermia and hyperoxia, have been studied for the treatment of brain injury. Treatment with magnesium and hypothermia has shown favorable outcome in rats with cerebral ischemia. We conclude that coadministration of magnesium and mannitol with pharmacological and physiological agents could be an effective neuroprotective regimen for the treatment of TBI.

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Section: Preclinical Studies With Magnesium In Brain Injurymentioning

confidence: 99%

Use of Magnesium in Traumatic Brain Injury

Sen¹,

Gulati

2010

Neurotherapeutics

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“…Decline in Mg 2ϩ has been associated with adverse outcomes, and administration of Mg 2ϩ salts improves cellular, biochemical, and functional outcomes after TBI. [61][62][63] In a rodent focal ischemia model, the NK 1 receptor antagonist SR140333 also significantly reduced infarct volume, implying that SP might play a role in exacerbating ischemic damage. 64 Turner and Vink 65 subsequently demonstrated in a rat transient middle cerebral artery occlusion model that NK 1 receptor antagonists given at 4 h after induction of ischemia can reduce BBB permeability and brain edema.…”

Section: Figmentioning

confidence: 99%

Substance P Antagonists as a Therapeutic Approach to Improving Outcome Following Traumatic Brain Injury

Vink

Heuvel

2010

Neurotherapeutics

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Summary:Although a number of secondary injury factors are known to contribute to the development of morphological injury and functional deficits following traumatic brain injury, accumulating evidence has suggested that neuropeptides, and in particular substance P, may play a critical role. Substance P is released early following acute injury to the CNS as part of a neurogenic inflammatory response. In so doing, it facilitates an increase in the permeability of the bloodbrain barrier and the development of vasogenic edema. At the cellular level, substance P has been shown to directly result in neuronal cell death; functionally, substance P has been implicated in learning and memory, mood and anxiety, stress mechanisms, emotion-processing, migraine, emesis, pain, and seizures, all of which may be adversely affected after brain injury. Inhibition of post-traumatic substance P activity, either by preventing release or by antagonism of the neurokinin-1 receptor, has consistently resulted in a profound decrease in development of edema and marked improvements in functional outcome. This review summarizes the current evidence supporting a role for substance P in acute brain injury.

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“…This analysis was limited, however, by the lack of randomization of the neuroprotective agent and standardization of techniques. 7 Likewise, despite promising preclinical data, 8 randomized clinical trials of magnesium sulfate did not result in better neurologic outcomes in clinical trials in acute stroke or traumatic brain injury. 9,10 To date, we are lacking in large prospective randomized trials of neuroprotection in humans.…”

Section: The Challenges Of Translating Animal Data To Patientsmentioning

confidence: 99%