Minocycline protects motor but not autonomic neurons after cauda equina injury.
Conus medullaris/cauda equina injuries typically result in loss of bladder, bowel, and sexual functions, partly as a consequence of autonomic and motor neuron death. To mimic these injuries, we previously developed a rodent lumbosacral ventral root avulsion (VRA) injury model, where both autonomic and motor neurons progressively die over several weeks. Here, we investigate whether minocycline, an antibiotic with putative neuroprotective effects, may rescue degenerating autonomic and motor neurons after VRA injury. Adult female rats underwent lumbosacral VRA injuries followed by a 2-week treatment with either minocycline or vehicle injected intraperitoneally. The sacral segment of the spinal cord was studied immunohistochemically using choline acetyltransferase (ChAT) and activated caspase-3 at 4 weeks post-operatively. Minocycline increased the survival of motoneurons but not preganglionic parasympathetic neurons (PPNs). Further investigations demonstrated that a larger proportion of motoneurons expressed activated caspase-3 compared to PPNs after VRA injury and indicated an association with minocycline's differential neuroprotective effect. Our findings suggest that minocycline may protect degenerating motoneurons and expand the therapeutic window of opportunity for surgical repair of proximal root lesions affecting spinal motoneurons.
Hoang
Thao X
TX
Department of Neurology, David Geffen School of Medicine at UCLA, Neuroscience Research Building, 635 Charles E. Young Drive South, Los Angeles, CA 90095-7334, USA.
Akhavan
Mahnaz
M
Wu
Jun
J
Havton
Leif A
LA
D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002420:Cauda Equina / Q000473:pathology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D008911:Minocycline / Q000627:therapeutic use*; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018696:Neuroprotective Agents; D002795:Choline O-Acetyltransferase; D053148:Caspase 3; D008911:Minocycline