Experimental neurology
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Experimental neurology · May 2000
Persistent neuroprotection with prolonged postischemic hypothermia in adult rats subjected to transient middle cerebral artery occlusion.
Postischemic hypothermia provides long-lasting neuroprotection against global cerebral ischemia in adult rats and gerbils. Studies indicate that hypothermia must be prolonged (e.g., 24 h) to indefatigably salvage hippocampal CA1 neurons. Delayed hypothermia also reduces focal ischemic injury. ⋯ Delayed hypothermia treatment significantly reduced cortical injury to 10% +/- 10 SD (P < 0.001) while striatal injury was marginally reduced to 79% loss +/- 17 SD (P < 0.05). Delayed hypothermia of only 34 degrees C provided long-lasting cortical and striatal protection in adult rats subjected to a severe MCAo insult. These results strongly support the clinical assessment of hypothermia in acute stroke.
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Experimental neurology · Apr 2000
Nerve injury-induced mechanical but not thermal hyperalgesia is attenuated in neurokinin-1 receptor knockout mice.
Mice lacking the gene encoding for substance P and neurokinin A, or the NK-1 receptor, exhibit alterations in behavior to various acute nociceptive stimuli. However, behavioral responses of NK-1 mutant animals have not been well characterized in models of chronic pain. We studied the behavioral responses of NK-1 knockout and wild-type control mice to thermal and mechanical stimuli before and after inducing chronic neuropathic pain by unilateral ligation of the L5 spinal nerve. ⋯ Similarly, the increase in withdrawal frequency to the cooling stimuli following the nerve injury was not different in the NK-1 knockout and wild-type mice. Mechanical hyperalgesia in the wild-type mice was not reversed by systemic administration of phentolamine, suggesting that the pain is not sympathetically maintained. The results indicate that NK-1 receptors contribute to the development of mechanical, but not thermal, hyperalgesia in neuropathic pain.
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Experimental neurology · Apr 2000
Comparative StudyEffect of axotomy on expression of NPY, galanin, and NPY Y1 and Y2 receptors in dorsal root ganglia and the superior cervical ganglion studied with double-labeling in situ hybridization and immunohistochemistry.
Using double-labeling techniques for both in situ hybridization and immunohistochemistry some peptides and peptide receptors were studied quantitatively in a sensory and a sympathetic ganglion after axotomy. In the lumbar 5 dorsal root ganglion (DRG) normally no neuropeptide Y- and only a few galanin-positive cell bodies are seen. Following complete transection of the sciatic nerve around 60% of all neuropeptide Y (NPY) neuron profiles (NPs) were galanin positive (+) and 33-44% of all galanin NPs were NPY(+). ⋯ However, the immunohistochemical analysis in the SCG demonstrated much lower numbers of peptide-positive neurons than seen with in situ hybridization, suggesting that the latter technique is more sensitive. The fact that a considerable number of neurons express NPY together with Y1- and/or Y2-Rs indicates that both receptors may act as autoreceptors, the Y1-R presumably at the level of the cell body and the Y2-R on nerve terminals in the dorsal horn and/or the periphery. The present results also show that in both sensory and sympathetic neurons there is a strong upregulation of the Y2-R after nerve injury, suggesting a possible role in trophic and regenerative events.
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Experimental neurology · Mar 2000
Diffusion and high resolution MRI of traumatic brain injury in rats: time course and correlation with histology.
Although widely employed in studies of cerebral ischemia, the use of diffusion-weighted imaging (DWI) for traumatic brain injury (TBI) has been both limited and primarily confined to the first few hours after injury. Therefore, the present study examined the temporal evolution of magnetic resonance imaging (MRI) signal changes from hours to weeks after moderate fluid-percussion TBI in rats. We used isotropic diffusion along three directions and high resolution (HR) spin-echo pulse sequences to visualize DWI and HR MRI changes, respectively. ⋯ Furthermore, the study showed that DWI was sensitive to MR signal change at 1-2 h post TBI (in select ROIs), whereas HR scans showed MR signal change primarily at later time points (3-4 h and later). Moreover, regions which demonstrate late changes are associated with histological damage and neurological impairment. The study demonstrates the utility of MRI to detect early changes, in some cases, that are predictive of long-lasting damage verified histologically.
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Experimental neurology · Feb 2000
Growth factors in combination, but not individually, rescue rd mouse photoreceptors in organ culture.
The rd mouse retina is an animal model for human retinal dystrophy in which the rod photoreceptors undergo apoptosis during the first 4 weeks in vivo or in organ culture. We have examined the effect of different families of trophic factors on the survival of rd mouse photoreceptors in organ culture. Retinas were harvested from rd mice at postnatal day 2 and grown in organ culture for 27 days in vitro (DIV) in DMEM with 10% fetal calf serum. ⋯ A significant increase in photoreceptor survival was seen with forskolin added to CNTF, but not to BDNF, FGF2, or GDNF. These results demonstrate that trophic factors promote photoreceptor survival through a synergistic interaction. Increased understanding of receptor interactions and signaling pathways may lead to a potential therapeutic role for combinatorial trophic factors in treatment of photoreceptor dystrophies.