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August 21, 1996, Vol 276, No. 7 >
ARTICLE | August 21, 1996

Pharmacologic Treatment of Acute Traumatic Brain Injury FREE

Alan I. Faden, MD
[+] Author Affiliations

Reprints: Alan I. Faden, MD, Georgetown University Medical Center, Institute for Cognitive and Computational Sciences, Research Building, 3970 Reservoir Road NW, Washington, DC 20007.


JAMA. 1996;276(7):569-570. doi:10.1001/jama.1996.03540070065034
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References

During the past several years, results of clinical trials have generated considerable optimism about the prospects for effective treatment of acute central nervous system (CNS) injuries. A multicenter trial demonstrated the effectiveness of methylprednisolone, as well as naloxone hydrochloride, in improving neurologic recovery after spinal cord injury.1 In ischemic stroke, early treatment with tissue plasminogen activator2 or treatment with low-molecular-weight heparin3 led to improved outcome for some patients. To date, however, no effective pharmacotherapy has been developed for head injury.

One of the more promising experimental strategies for treatment of acute CNS injury has been the use of antioxidants or free-radical scavengers. This approach is based on the concept that oxygen free radicals are generated in response to the insult, thereby overwhelming endogenous antioxidant or free radical-scavenging systems such as superoxide dismutase (SOD), catalase, glutathione, ascorbic acid, and α-tocopherol.4,5 Free radicals are believed to contribute to

REFERENCES

1 +
Bracken MB, Holford TR.  Effects of timing of methylprednisolone or naloxone administration on recovery of segmental and long-track neurological function in NASCIS 2 . J Neurosurg . 1993;;79:500-507.
2 +
The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.  Tissue plasminogen activator for acute ischemic stroke . N Engl J Med . 1995;;333:1581-1587.
3 +
Kay R, Wong KS, Yu YL, et al.  Low molecular-weight heparin for the treatment of acute ischemic stroke . N Engl J Med . 1995;;333:1588-1593.
4 +
Chan PH.  Role of oxidants in ischemic brain damage . Stroke . 1996;;27:1124-1129.
5 +
Faden AI.  Pharmacological treatment of central nervous system trauma . Pharmacol Toxicol . 1996;;78:12-17.
6 +
Hall ED, Braughler JM.  Free radicals and lipid peroxidation . In: Narayan RK, Wilberger JE, Povlishock JT, eds. Neurotrauma . New York, NY: McGraw-Hill Book Co; 1996;:1405-1419.
7 +
Muizelaar JP, Marmarou A, Young HF, et al.  Improving the outcome of severe head injury with the oxygen radical scavenger polyethylene glycol conjugated superoxide dismutase: a phase II trial . J Neurosurg . 1993;;78:375-382.
8 +
Young B, Runge JW, Waxman KS, et al.  Effects of pegorgotein on neurologic outcome of patients with severe head injury: a multicenter, randomized controlled trial . JAMA . 1996;;276:538-543.
9 +
Chan PH, Kamii H, Yang G, et al.  Brain infarction is not reduced in SOD-1 transgenic mice after a permanent focal brain ischemia . Neuroreport . 1993;;5: 293-296.
10 +
Marshall LF, Marshall SB.  Pitfalls and advances from the international tirilazed trial in moderate and severe head injury . Neurotrauma . 1995;;12:929-932.
11 +
Bullock R.  Experimental drug therapies for head injury . In: Narayan RK, Wilberger JE, Povlishock JT, eds. Neurotrauma . New York, NY: McGraw-Hill Book Co; 1996;:375-391.
12 +
Alves W, Eisenberg HM.  Head injury trials—past and present . In: Narayan RK, Wilberger JE, Povlishock JT, eds. Neurotrauma . New York, NY: McGraw-Hill Book Co; 1996;:947-967.
13 +
Harders A, Kakarieka A, Braakman R, and the German tSAH Study Group.  Traumatic subarachnoid hemorrhage and its treatment with nimodipine . J Neurosurg . 1996;;85:82-89.
14 +
Teasdale G, Bailey I, Bell A, and the British/Finnish Cooperative Head Injury Trial Group.  The effect of nimodipine on outcome after head injury: a prospective randomized controlled trial . Acta Neurochir (Wien) . 1990;;51:315-316.
15 +
European Study Group on Nimodipine in Severe Head Injury.  A multicenter trial of the efficacy of nimodipine on outcome after severe head injury . J Neurosurg . 1994;;80:797-804.
16 +
Pitts LH, Ross A, Chase GA, Faden AI.  Treatment with thyrotropinreleasing hormone (TRH) in patients with traumatic spinal cord injuries . J Neurotrauma . 1995;;12:235-243.
17 +
Belayev L, Busto R, Zhao W, Ginsberg MD.  HU-211, a novel non-competitive NMDA antagonist, improves neurological deficit and reduces infarct volume after reversible focal cerebral ischemia in the rat . Stroke . 1995;;26:2313-2320.
18 +
Biegon A, Bar-Joseph A.  Development of HU-211 as a neuroprotectant for ischemic brain damage . Neurol Res . 1995;;17:275-280.
19 +
Young W.  Spinal cord injury therapy and Multicenter Acute Spinal Cord Injury Study (MASCIS) . J Neurotrauma . 1995;;3:349.

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Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Bracken MB, Holford TR.  Effects of timing of methylprednisolone or naloxone administration on recovery of segmental and long-track neurological function in NASCIS 2 . J Neurosurg . 1993;;79:500-507.
2 +
The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.  Tissue plasminogen activator for acute ischemic stroke . N Engl J Med . 1995;;333:1581-1587.
3 +
Kay R, Wong KS, Yu YL, et al.  Low molecular-weight heparin for the treatment of acute ischemic stroke . N Engl J Med . 1995;;333:1588-1593.
4 +
Chan PH.  Role of oxidants in ischemic brain damage . Stroke . 1996;;27:1124-1129.
5 +
Faden AI.  Pharmacological treatment of central nervous system trauma . Pharmacol Toxicol . 1996;;78:12-17.
6 +
Hall ED, Braughler JM.  Free radicals and lipid peroxidation . In: Narayan RK, Wilberger JE, Povlishock JT, eds. Neurotrauma . New York, NY: McGraw-Hill Book Co; 1996;:1405-1419.
7 +
Muizelaar JP, Marmarou A, Young HF, et al.  Improving the outcome of severe head injury with the oxygen radical scavenger polyethylene glycol conjugated superoxide dismutase: a phase II trial . J Neurosurg . 1993;;78:375-382.
8 +
Young B, Runge JW, Waxman KS, et al.  Effects of pegorgotein on neurologic outcome of patients with severe head injury: a multicenter, randomized controlled trial . JAMA . 1996;;276:538-543.
9 +
Chan PH, Kamii H, Yang G, et al.  Brain infarction is not reduced in SOD-1 transgenic mice after a permanent focal brain ischemia . Neuroreport . 1993;;5: 293-296.
10 +
Marshall LF, Marshall SB.  Pitfalls and advances from the international tirilazed trial in moderate and severe head injury . Neurotrauma . 1995;;12:929-932.
11 +
Bullock R.  Experimental drug therapies for head injury . In: Narayan RK, Wilberger JE, Povlishock JT, eds. Neurotrauma . New York, NY: McGraw-Hill Book Co; 1996;:375-391.
12 +
Alves W, Eisenberg HM.  Head injury trials—past and present . In: Narayan RK, Wilberger JE, Povlishock JT, eds. Neurotrauma . New York, NY: McGraw-Hill Book Co; 1996;:947-967.
13 +
Harders A, Kakarieka A, Braakman R, and the German tSAH Study Group.  Traumatic subarachnoid hemorrhage and its treatment with nimodipine . J Neurosurg . 1996;;85:82-89.
14 +
Teasdale G, Bailey I, Bell A, and the British/Finnish Cooperative Head Injury Trial Group.  The effect of nimodipine on outcome after head injury: a prospective randomized controlled trial . Acta Neurochir (Wien) . 1990;;51:315-316.
15 +
European Study Group on Nimodipine in Severe Head Injury.  A multicenter trial of the efficacy of nimodipine on outcome after severe head injury . J Neurosurg . 1994;;80:797-804.
16 +
Pitts LH, Ross A, Chase GA, Faden AI.  Treatment with thyrotropinreleasing hormone (TRH) in patients with traumatic spinal cord injuries . J Neurotrauma . 1995;;12:235-243.
17 +
Belayev L, Busto R, Zhao W, Ginsberg MD.  HU-211, a novel non-competitive NMDA antagonist, improves neurological deficit and reduces infarct volume after reversible focal cerebral ischemia in the rat . Stroke . 1995;;26:2313-2320.
18 +
Biegon A, Bar-Joseph A.  Development of HU-211 as a neuroprotectant for ischemic brain damage . Neurol Res . 1995;;17:275-280.
19 +
Young W.  Spinal cord injury therapy and Multicenter Acute Spinal Cord Injury Study (MASCIS) . J Neurotrauma . 1995;;3:349.

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