As indicated in Figure 11, multiple inflammatory processes play a role in secondary injury and perhaps repair in stroke, TBI, and SCI. First of all, the arachidonic acid cascade is activated, resulting in the formation of various deleterious prostanoids and leukotrienes. COX-1 and -2 inhibitors can decrease the formation of PGF2a and TXA2, and have neuroprotective effects.42
In addition to this acute inflammatory mechanism initiated in the first minutes of the insult, a more delayed microglial and astrocyte activation and influx of neutrophils, monocytes, and T lymphocytes has been documented to
begin within the first hour. Some of this cellular inflammatory response appears to continue for weeks and perhaps months, and may play a role in both secondary damage and repair processes.74 Considerable evidence exists to support the idea that much of this cellular inflammation can amplify the secondary injury process, and therefore should be inhibited via anti-inflammatory, immunosuppressive, or antiproliferative agents. With regard to the latter mechanistic possibility, a recent study in a rodent TBI model has shown that there is a considerable posttraumatic increase in cell cycle proteins, many of which have kinase activities.75 In the same study, the administration of the cell cycle inhibitor flavoperidol decreased posttraumatic elevations in neuronal and astrocyte cyclin D1 expression, reduced neuronal damage and astrocyte proliferation, and improved neurological recovery.
In the context of SCI models, the second-generation tetracycline derivative minocycline is neuroprotective and improves neurological recovery, together with suppressing microglial activation.76,77 However, there is ongoing controversy as to whether the cellular inflammation is more bad than good for the injured spinal cord, or vice versa.
Some believe that enhancement of cellular inflammation begun after the first 24 h may act to stimulate repair
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