dizocilpine-maleate and Hematoma

Fibrinolytic therapy for spontaneous intracerebral hemorrhage using recombinant tissue plasminogen activator (rtPA) is considered a viable alternative to microsurgical hematoma removal. However, experimental data suggest that rtPA is neurotoxic and evokes a late perihematomal edema. We present preliminary data focusing on the avoidance of late edema formation after lysis of an intracerebral hematoma in a porcine model.. Twenty pigs underwent placement of a frontal intracerebral hematoma with a minimum volume of 1 mL. Half of the pigs were subjected to rtPA clot lysis and MK-801 injection for blockage of the NMDA receptor-mediated rtPA-enhanced excitotoxic pathway. The remaining 10 pigs received desmoteplase (DSPA) for clot lysis, which is known to be a less neurotoxic fibrinolytic agent than rtPA. MRI on the day of surgery and on postoperative days 4 and 10 was used to assess hematoma and edema volumes.. Late edema formation could be prevented in both the MK-801/rtPA and DSPA pigs.. The benefits of fibrinolytic therapy for intracerebral hematomas appear to be counterbalanced by late edema formation. MK-801 infusion as an adjunct to rtPA lysis, or the use of DSPA instead of rtPA, prevents late edema and therefore has the potential to further improve results after clot lysis.

Topics: Animals; Brain Edema; Cerebral Hemorrhage; Disease Models, Animal; Dizocilpine Maleate; Hematoma; Magnetic Resonance Imaging; Neuroprotective Agents; Plasminogen Activators; Swine; Thrombolytic Therapy; Time Factors

The aims of this study were to clarify the histological and histochemical changes associated with cell death in the spinal cord after acute traumatic injury and to examine the role of excitatory amino acid release mediated by N-methyl-D-aspartate (NMDA) receptors.. Following laminectomy, the spinal cord in 70 rats was injured at the T-9 level by applying extradural static weight-compression, in which a cylindrical compressor was used to induce complete and irreversible transverse spinal cord injury (SCI) with paralysis of the lower extremities. The injured rats were killed between 30 minutes and 14 days after injury, and the injured cord was removed en bloc. Rats that received NMDA receptor antagonist (MK-801) were killed at the same time points as those that received saline. The specimens were stained with hematoxylin and eosin, Nissl, and Klüver-Barrera Luxol fast blue and subjected to in situ nick-end labeling, a specific in situ method used to allow visualization of apoptosis. Thirty minutes post-SCI, a large hematoma was observed at the compressed segment. Six hours after injury, large numbers of dead cells that were not stained by in situ nick-end labeling were observed. Between 12 hours and 14 days postinjury, nuclei stained by using the in situ nick-end labeling technique were observed not only at the injury site but also in adjoining segments that had not undergone mechanical compression, suggesting that the delayed cell death was due to apoptosis. The number of cells stained by in situ nick-end labeling was maximum at 3 days postinjury. The results of electron microscopic examination were also consistent with apoptosis. In the MK-801-treated rats, the number of cells stained by in situ nick-end labeling was smaller than in nontreated rats at both 24 hours and 7 days after injury.. These findings suggest that NMDA-receptor activation promotes delayed neuronal and glial cell death due to apoptosis.

Topics: Animals; Apoptosis; Cell Count; Cell Death; Cell Nucleus; Coloring Agents; Demyelinating Diseases; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Fluorescent Dyes; Hematoma; In Situ Nick-End Labeling; Laminectomy; Male; Microscopy, Electron; N-Methylaspartate; Nerve Fibers, Myelinated; Neurons; Neuroprotective Agents; Paralysis; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate; Spinal Cord Compression; Spinal Cord Injuries