The novel pyrrolopyrimidine PNU-101033-E improves facial motor neuron survival following intracranial axotomy of the facial nerve in the adult rat.
Neuronal survival is important to functional restitution following axotomy. Proximal lesions of the facial nerve, due to head trauma or tumor growth, for example, may cause long-standing or even permanent facial nerve palsy. Betamethasone has been used by several neurosurgical clinics for the treatment of postoperative facial nerve palsy; however, this practice is based only on clinical experience. The aim of the present study was to explore the putative effect on facial motor neuron survival of a novel lazaroid (pyrrolopyrimidine, PNU-101033-E) and furthermore to compare the effects with those of betamethasone, following intracranial transection of the facial nerve in adult rats. Both agents are known to inhibit lipid peroxidation by free radical scavenging. The lesion model used has recently been reported to induce massive neuronal cell death with a relative survival of 26.8 +/- 11.3% 1 month after lesion. Oral administration of lazaroids or daily injections of betamethasone followed surgery for 1 month, after which quantification of motor neuronal profiles was performed in the facial nucleus. Lazaroid-treated animals showed a significantly enhanced neuronal survival (68.0 +/- 9.8%), whereas no significant difference was found in betamethasone-treated animals (33.1 +/- 11.7%). The microglial and astrocytic responses in the facial nucleus were intense on the operated sides in betamethasone-treated as well as lazaroid-treated animals, and no differences in comparison with untreated animals were found. In conclusion, we found that the novel pyrrolopyrimidine PNU-101033-E, but not betamethasone, significantly enhanced nerve cell survival. This agent may therefore serve as a useful neuroprotective agent following intracranial trauma to the facial nerve and should be further evaluated for clinical use.
Mattsson
P
P
Karolinska Hospital, Department of Clinical Neuroscience, Section for Neurosurgery, Stockholm, Sweden. perm@neuro.ks.se
Aldskogius
H
H
Svensson
M
M
D000818:Animals; D019771:Axotomy; D001623:Betamethasone / Q000627:therapeutic use*; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D005154:Facial Nerve / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009046:Motor Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018696:Neuroprotective Agents; C112281:PNU 101033E; D011743:Pyrimidines; D011758:Pyrroles; D001623:Betamethasone