Large-scale cortical reorganization following forelimb deafferentation in rat does not involve plasticity of intracortical connections.

Physiological mapping of the body representation 1 month or longer after forelimb removal in adult rats revealed new pockets of shoulder representation in the forepaw barrel subfield (FBS) in the first somatosensory cortex (SI). These "new" shoulder representations have longer evoked response latencies than sites in the shoulder representation within the trunk subfield, hereafter referred to as the "original" shoulder representation. We postulated that the "new" shoulder representations in the FBS were relayed from the "original" shoulder representation. We investigated this hypothesis by studying anatomical connectivity between the "original" shoulder representation and the FBS in intact control and forelimb deafferented adult rats using Phaseolus vulgaris leucoagglutinin (PHA-L), biocytin, and biotin dextran-amine (BDA) as anterograde tracers. The retrograde tracer cholera toxin beta subunit (CT-B) injected into the FBS was also used to study connectivity between the "original" shoulder representation and the FBS. Using these anatomical tracing techniques, we were unable to show the existence of a direct corticocortical connection between the "original" shoulder representation in the trunk subfield and the FBS in either intact or deafferented rats. Functional connectivity between the two cortical regions was studied by ablating the "original" shoulder representation alone or in combination with the shoulder representation in the second somatosensory cortex (SII) while recording evoked responses in the FBS following electrical stimulation of the shoulder. Both ablations failed to eliminate the evoked responses at the "new" shoulder sites in the FBS, suggesting that SI and SII are not necessary for "new" shoulder input in the FBS. It is suggested that subcortical sites may play a major role in large-scale cortical reorganization. Results of projections from the "original" shoulder representation to parietal medial (PM), parietal lateral (PL), SII, parietal ventral (PV), and parietal rhinal (PR) sensory fields and agranular lateral (AgL) and agranular medial (AgM) motor fields are also described.

Thalamocortical arbors extend beyond single cortical barrels: an in vivo intracellular tracing study in rat.

Neurons in layer IV of rat somatosensory (SI) barrel cortex receive punctate somatic input from well-defined regions of the periphery. Following peripheral deafferentation, SI neurons in deafferented cortex respond to new input from neighboring regions of the skin surface. The precise mechanism(s) through which this occurs is unknown, although corticocortical and barreloid to barrel connections have been suggested as possible substrates. Because layer-IV barrels receive a strong afferent input from ventroposterior (VP) thalamic projection neurons, any divergence in the thalamocortical (TC) projection to multiple cortical barrels could also provide an anatomical substrate for rapid cortical reorganization. We used in-vivo intracellular recording methods to record and physiologically identify neurons in rat VP and to label those neurons with an intracellular tracer. Thalamic neurons (n=117) were impaled with sharp intracellular electrodes, and the receptive field(s) and firing pattern were measured. Cells were then injected with biocytin or biotinylated dextran amine (BDA). A total of 38 labeled TC neurons were quantitatively analyzed for soma size and dendritic arborization size; quantitative analysis of TC-axon arborizations in layer IV of barrel cortex was carried out in a total of 13 TC neurons. Two different axon-arborization patterns were identified in SI cortex: direct-projecting axons (n=6) were observed to project to and arborize within a single cortical barrel as well as extend their fibers into adjacent barrels; bifurcating-type axons (n=7) were seen to bifurcate in the subcortical white matter or in layer VI and then project to multiple barrel columns, where they arborized in layer IV. Axon fibers were always observed in three or more cortical barrels (mean=5, range=3-7). The mean mediolateral extent of arborizations in layer IV for the direct-projecting and bifurcating type axons were 458 microm and 1,302 microm, respectively, and these were significantly different (t=3.78, P<0.01). Axon-fiber length within cortical laminae was measured for each arborization pattern in relationship to the total fiber length within a cortical column. Direct-projecting axons always had greater than 50% of their fiber length within layer IV. Bifurcating-type axons were differentially distributed within multiple columns and always had less than 50% of their total column fiber length in layer IV. Morphological analysis of TC somata and dendrites revealed no correlation between local neuron morphology and axonal-arborization patterns. All intracellularly recorded TC neurons had similar adapting firing patterns when injected with a long-duration pulse. Our results showed that TC neurons project to multiple cortical barrels with one barrel receiving the principal input. This divergent TC projection pattern in SI cortex may provide an anatomical substrate for cortical plasticity and must be considered in any mechanism of rapid cortical reorganization.

Evaluation of resorbable barriers for preventing surgical adhesions.

OBJECTIVE: To evaluate the ability of collagen film, collagen gel, sodium hyaluronate/carboxymethylcellulose film, and fibrin glue to prevent adhesion formation. DESIGN: Randomized trial using a rat model of a standardized abdominal wound and cecal wound. SETTING: University research laboratory. ANIMAL(S): Sprague-Dawley female rats. INTERVENTION(S): Resorbable barriers or no barrier (controls) were placed between an abdominal wall wound (1 cm x 2 cm) and a similarly sized cecal wound. MAIN OUTCOME MEASURE(S): Adhesion formation between wounds was assessed and quantitated 7 days after surgery. RESULT(S): Without treatment, 34 of 35 untreated rats (97%) developed adhesions. Treatment with collagen gel (3 of 33 rats), collagen film (3 of 10 rats), or sodium hyaluronate/carboxymethylcellulose film (2 of 10 rats) significantly reduced the incidence of adhesion formation. Treatment with fibrin sealant resulted in 9 of 10 animals having adherent wounds 7 days after surgery. CONCLUSION(S): Resorbable barriers of collagen gel, collagen films and sodium hyaluronate/carboxymethylcellulose film were effective in significantly reducing adhesion formation. Fibrin sealant at 7 days had an incidence of adhesion formation similar to that in untreated control animals.

Serotonergic modulation of hyperpolarization-activated current in acutely isolated rat dorsal root ganglion neurons.

1. The effect of serotonin (5-HT) on the hyperpolarization-activated cation current (IH) was studied in small-, medium- and large-diameter acutely isolated rat dorsal root ganglion (DRG) cells, including cells categorized as type 1, 2, 3 and 4 based on membrane properties. 5-HT increased IH in 91 % of medium-diameter DRG cells (including type 4) and in 67 % of large-diameter DRG cells, but not other DRG cell types. 2. The increase of IH by 5-HT was antagonized by spiperone but not cyanopindolol, and was mimicked by 5-carboxyamidotryptamine, but not (+)-8-hydroxydipropylaminotetralin (8-OH-DPAT) or cyanopindolol. These data suggested the involvement of 5-HT7 receptors, which were shown to be expressed by medium-diameter DRG cells using RT-PCR analysis. 3. 5-HT shifted the conductance-voltage relationship of IH by +6 mV without changing peak conductance. The effects of 5-HT on IH were mimicked and occluded by forskolin, but not by inactive 1,9-dideoxy forskolin. 4. At holding potentials negative to -50 mV, 5-HT increased steady-state inward current and instantaneous membrane conductance (fast current). The 5-HT-induced inward current and fast current were blocked by Cs+ but not Ba2+ and reversed at -23 mV, consistent with the properties of tonically activated IH. 5. In medium-diameter neurons recorded from in the current clamp mode, 5-HT depolarized the resting membrane potential, decreased input resistance and facilitated action potential generation by anode-break excitation. 6. The above data suggest that in distinct subpopulations of DRG neurons, 5-HT increases cAMP levels via activation of 5-HT7 receptors, which shifts the voltage dependence of IH to more depolarized potentials and increases neuronal excitability.

A new silver sulfadiazine water soluble gel.

Silver sulfadiazine is the most commonly used topical antibacterial agent for the treatment of burn wounds. It has many clinical advantages, including a broad spectrum of antimicrobial activity, low toxicity, and minimal pain on application. The current formulation of silver sulfadiazine contains a lipid soluble carrier, polypropylene glycol, that has certain disadvantages, including pseudo-eschar formation and the need for twice daily application. The purpose of this investigation was to describe a new formulation of silver sulfadiazine in a water soluble gel, poloxamer 188. The antibacterial activity of this new gel has been compared to that of the commercially available silver sulfadiazine cream by in vitro and in vivo testing. The results of the in vitro antibacterial testing of these two different agents demonstrated the superiority of the new gel formulation. In experimental wounds, the antibacterial activity of the gel and the commercially available silver sulfadiazine cream were not significantly different when applied once a day. The antibacterial activity of the gel when applied once a day was comparable to that encountered by twice daily applications of the silver sulfadiazine cream by experimental wounds. The major advantage of this gel was its ease of application and removal that is attributed to its water solubility.

Functional electric stimulation: its efficacy and safety in improving pulmonary function and musculoskeletal fitness.

The efficacy and safety of functional electric stimulation (FES) in improving cardiovascular and musculoskeletal fitness in individuals with spinal cord injury was evaluated. Ten males and two females aged 16 to 46 years began an FES program from three months to 22 years after injury. Seven patients had paraplegia and five had quadriplegia. The FES protocol consisted of three phases: (1) leg extension, the stimulation of the quadriceps muscle group only, first without and then with weights; (2) ergometry, the stimulation of quadriceps, hamstrings, and gluteal muscles to produce a bicycling motion; and (3) resistance, the addition of resistance during the bicycling motion described in phase 2. Values for tidal volume, oxygen consumption, and the respiratory quotient were obtained during each phase. Tidal volume and oxygen consumption levels increased significantly (p less than .001) from the start of FES to both the ergometry and the resistance phases. The respiratory quotient improved significantly (p less than .001) from the start of FES to resistance but not from the start of FES to ergometry. Thigh and calf girths were measured at the start of FES and during resistance. Thigh girths increased significantly from the beginning of the program to the resistance phase, p less than .002 for the right leg and p less than .001 for the left. Calf girth, however, showed no significant increase. Based on these improvements and the absence of any serious complications, we believe that FES is an effective and safe method to improve cardiovascular and musculoskeletal fitness in individuals with spinal cord injury.