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Following infection of dissociated embryonic day 13 rat medullary raphe cells with a retrovirus encoding the temperature-sensitive mutant of SV40 large T-antigen (T-ag), a neuronal cell line, RN46A, was cloned by serial dilution. At 33 degrees C, RN46A cells express nuclear T-ag immunoreactivity and divide with a doubling time of 9 hr. Undifferentiated RN46A cells express low levels of neuron-specific enolase (NSE) and low (NF-L)-and medium (NF-M)- but not high (NF-H)- molecular-weight neurofilament proteins. Under differentiation conditions, RN46A cells cease dividing, take on a neuronal morphology, and express enhanced levels of NSE and all three NF proteins. Elevation of intracellular cAMP levels increases neurofilament protein expression, whereas activators of various other intracellular second messenger systems have no effect. Differentiated RN46A cells express low-affinity nerve growth factor (NGF) receptor (p75NGFR) and are immunoreactive using an antibody that recognizes the carboxy-terminal 13 amino acids of all three trk proteins (pan-trk). Both immunoreactivities could be potentiated by treatment with brain-derived neurotrophic factor (BDNF), NGF, and adrenocorticotropic hormone, fragment 4–10 (ACTH4–10). Differentiated RN46A cells express low levels of tryptophan hydroxylase (TPH) immunoreactivity, which could be enhanced by treatment with ACTH4–10, BDNF, or NGF. Low levels of serotonin immunoreactivity are detected in differentiated RN46A cells, and this was potentiated by differentiating RN46A cells with BDNF for 8 d and 40 mM KCl for days 4–8. HPLC analysis confirmed these immunohistochemical data. RN46A cells should prove useful to elucidate intracellular mechanisms that control neurofilament assembly and 5-HT expression in differentiating raphe neurons.

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SummaryLeft ventricular (LV) myocardial atrophy and diminished cardiac function have been shown to accompany chronic human tetraplegia. These changes are attributable both to physical immobilisation and abnormal autonomic circulatory regulation imposed by a spinal cord injury (SCI). To test whether exercise training increases LV mass following chronic SCI, 8 neurologically complete quadriplegic males at 2 SCI rehabilitation and research centres underwent one month of electrically-stimulated quadriceps strengthening followed by 6 months of electrically-stimulated cycling exercise. Resting M-mode and 2-D echocardiograms were measured before and after exercise training to quantify the interventricular septal and posterior wall thicknesses at end-diastole (IVST ED and PWT ED, respectively), and the LV internal dimension at end-diastole (L VI D ED). LV mass was computed from these measurements using standard cube function geometry. Results showed a 6·5% increase in LVIDED foliowing exercise training (p<0·02), with increases in IVSTED and PWTED of 17·8 (p<0·002) and 20·3% (p

Dysfunction of spinal motor conduction during surgical procedures may not be reflected by changes in somatosensory evoked potential waveforms. A method of monitoring that allows direct and continuous assessment of motor function within the central nervous system during surgery would be useful. This paper describes one such method utilizing noninvasive electric cortical stimulation to evoke muscle activity (the motor evoked potential, or MEP) during surgery. The effect of isoflurane (superimposed on a baseline of N2O/narcotic anesthesia) on MEP's in response to cortical stimulation is specifically examined. Eight patients undergoing elective neurosurgical operations were included in the study. All patients received a background of general anesthesia and partial nondepolarizing neuromuscular blockade. The motor cortex was stimulated electrically via self-adhesive scalp electrodes. Electromyographic responses from multiple muscles were measured with subdermal electroencephalograph-type needle electrodes. Motor responses to stimulation were continually recorded on magnetic tape for off-line analysis. Once closing of the surgical incision was begun, a series of four to five stimuli of constant magnitude were applied to obtain "baseline" MEP responses. Patients were then ventilated with isoflurane for up to 8 minutes, during which time stimuli were continued every 15 to 20 seconds. Comparison was made of MEP responses for trials before, 1 minute after, and 5 minutes after the addition of isoflurane. All patients demonstrated reproducible motor responses to cortical stimulation during surgery. Addition of isoflurane [isoflurane)exp, less than or equal to 0.5%) to pre-existing anesthesia caused marked attenuation of MEP amplitudes in all patients within 5 minutes of its application, without affecting neuromuscular transmission as judged by direct peripheral nerve stimulation. It is concluded that: 1) monitoring motor system integrity and function with electric transcranial cortical stimulation during surgery is feasible when utilizing an N2O/narcotic anesthetic protocol; and 2) the quality of data obtained will likely suffer with the addition of isoflurane.

Noninvasive transcranial magnetic stimulation (TMS) of the motor cortex was used to evoke electromyographic (EMG) responses in persons with spinal cord injury (n = 97) and able-bodied subjects (n = 20, for comparative data). Our goal was to evaluate, for different levels and severity of spinal cord injury, potential differences in the distribution and latency of motor responses in a large sample of muscles affected by the injury. The spinal cord injury (SCI) population was divided into subgroups based upon injury location (cervical, thoracic, and thoracolumbar) and clinical status (motor-complete versus motor-incomplete). Cortical stimuli were delivered while subjects attempted to contract individual muscles, in order to both maximize the probability of a response to TMS and minimize the response latency. Subjects with motor-incomplete injuries to the cervical or thoracic spinal cord were more likely to demonstrate volitional and TMS-evoked contractions in muscles controlling their foot and ankle (i.e., distal lower limb muscles) compared to muscles of the thigh (i.e., proximal lower limb muscles). When TMS did evoke responses in muscles innervated at levels caudal to the spinal cord lesion, response latencies of muscles in the lower limbs were delayed equally for persons with injury to the cervical or thoracic spinal cord, suggesting normal central motor conduction velocity in motor axons caudal to the lesion. In fact, motor response distribution and latencies were essentially indistinguishable for injuries to the cervical or thoracic (at or rostral to T10) levels of the spine. In contrast, motor-incomplete SCI subjects with injuries at the thoracolumbar level showed a higher probability of preserved volitional movements and TMS-evoked contractions in proximal muscles of the lower limb, and absent responses in distal muscles. When responses to TMS were seen in this group, the latencies were not significantly longer than those of able-bodied (AB) subjects, strongly suggestive of "root sparing" as a basis for motor function in subjects with injury at or caudal to the T11 vertebral body. Both the distribution and latency of TMS-evoked responses are consistent with highly focal lesions to the spinal cord in the subjects examined. The pattern of preserved responsiveness predominating in the distal leg muscles is consistent with a greater role of corticospinal tract innervation of these muscles compared to more proximal muscles of the thigh and hip.

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