Ontogeny of feline temporal lobe epilepsy, II: Stability of spontaneous sleep epilepsy in amygdala-kindled kittens.

We previously described a model of spontaneous "sleep epilepsy" in kindled kittens with temporal lobe epilepsy (TLE). We now describe the postkindling course of this model from preadolescence to maturity and suggest pathophysiologic mechanisms. Spontaneous epilepsy, particularly generalized tonic-clonic convulsions (GTCs), developed 1h to 4 months after amygdala kindling and persisted to adulthood. At first, GTCs were detected only in sleep; later, convulsions also occurred during wakefulness. Two factors were consistently associated with the sequential onset of sleep and waking GTCs: seizure clusters and anatomic seizure localization. (1) Seizure clusters. Cats with infrequent or unclustered GTCs continued to exhibit "sleep epilepsy," defined by convulsions occurring exclusively during sleep. In contrast, cats with frequent seizure clusters developed recurrent or terminal convulsive status in conjunction with GTCs during waking and sleep. Severe seizure manifestations therefore appeared to contribute to the dissociation of convulsions from the sleep-wake cycle. (2) Anatomical seizure localization. Focal seizure origin appeared to differentiate sleep from waking GTCs. Onset during sleep was first recorded in the kindled amygdala, whereas onset during waking was initially detected outside the temporal lobe. Findings thus suggest secondary "kindling" of multifocal epilepsy. Secondary epileptogenesis is consistent with "transsynaptic" kindling effects. This phenomenon is defined in mature animals by rapid secondary site kindling (transfer) and subtle morphologic changes distal to the stimulating electrode. Transfer may be accentuated by youth, because kittens developed spontaneous seizure foci in previously unstimulated tissue. Moreover, multifocal interactions and diffuse cell loss were implicated as possible mechanisms. Collectively, the findings indicate complications with early onset TLE in kindled cats. Onset during youth can have an unfavorable prognosis, reflected by recurrent status epilepticus and multifocal epilepsy with convulsions distributed throughout the sleep-wake cycle.

Spontaneous sleep epilepsy in amygdala-kindled kittens: a preliminary report.

We describe a model of 'sleep epilepsy' after amygdala kindling in kittens. Seizure activity was evaluated at different times in the sleep-wake cycle. Susceptibility was documented by thresholds for evoked convulsions in kittens without spontaneous seizures (n = 5) and by polygraphic or split-screen video recordings in kittens with spontaneous seizures (n = 6). There were 3 main findings: (1) subconvulsive seizures occurred randomly in waking and slow-wave-sleep (SWS); (2) convulsive seizure activity peaked during SWS, especially during the transition from SWS into rapid-eye-movement (REM) sleep; (3) generalized seizure activity was suppressed during stable REM sleep. Seizure patterns thus resemble clinical data designating convulsive temporal lobe epilepsy (TLE) the prototypic pure sleep epilepsy, whereas complex-partial TLE can occur at any time. Prominent secondary TLE generalization during the REM transition suggested involvement of brainstem regions which generate REM onset and innervate the temporal lobe. Adrenergic cells of the locus ceruleus discharge at progressively reduced rates during the transition into REM. Decreased norepinephrine release at this time might disinhibit epileptic neurons in the kindled focus, thus encouraging seizure propagation during the REM transition.

[Development of a small-lumen vascular prosthesis coated with autologous endothelial cells]. / Entwicklung einer kleinlumigen mit autologen Endothelzellen beschichteten Gefässprothese.

A new compliant prosthesis with a monolayer of autologous endothelial cells (ENC) has been developed. It consists of a porous polyurethane-siloxane-copolymer reinforced by a polyester network to prevent excessive dilatation. On the inner surface an ENC monolayer is established before implantation by a cell culture procedure. The prosthesis displays compliance (13.2 +/- 3.0 x 10(-4) mmHg-1) comparable to native arteries. It is non-kinkable (minimal radius of curvature less than 5 mm). Burst resistance, remaining deformation, cut out force and tensile strength are superior to standard values. ENC-coverage in excess of 95% of the inner surface was produced in vitro using a lining procedure. The monolayer of confluent cells was demonstrated to consist of endothelial cells by their characteristic cobblestone morphology, the expression of factor VIII related antigen and the specific uptake of Dil-Ac-LDL. The unstimulated prostacyclin production was similar both in native veins as well as in lined prostheses. Antithrombogenicity of the endothelial cell lining was demonstrated in 24 h animal implants.

A compliant small-diameter vascular prosthesis lined with functional venous endothelial cells.

The long-term patency of small-diameter vascular grafts is still unsatisfactory. In contrast to native arteries, they are inelastic and lack active antithrombogenicity. To improve long-term patency, a new 4 mm internal diameter prosthesis was developed which is compliant and lined with functional endothelial cells (ENC). The wall of this prosthesis consists of a microporous polyurethane-siloxane copolymer reinforced with a polyester network. It displays compliance (13.2 x 10(-4) mmHg-1) comparable to native arteries, is nonkinkable (minimum radius of curvature = 5 mm), burst resistant, and easily suturable. Using a lining procedure, coverage of prostheses by ENC was in excess of 95%. The ENC populations were found to be highly pure (by factor VIII-related antigen, DilAcLDL uptake) and to produce about 0.3 ng prostacyclin per cm2. In vitro tests of shear stress resistance demonstrated that ENC monolayers on the new elastic prosthesis remain intact for 3 hr in physiologically pulsating culture medium (Vmax = 50 cm/sec). Lined prostheses implanted for 24 hours in mongrel dogs as an arteriovenous shunt demonstrated the antithrombogenicity of the cultured ENC. The results suggest that small-diameter vascular prostheses which are compliant, porous, and actively antithrombogenic are feasible.