[Efficacy of Spirolept vaccine against human leptospirosis as estimated by passive protection of laboratory rodents]. / Etude de l'efficacité du vaccin Spirolept contre la leptospirose par la protection passive de rongeurs de laboratoire.

OBJECTIVE: This study had for aim to assess the serological response induced by the Spirolept vaccine against human leptospirosis. METHOD: A serological follow-up was made on 31 patients at a risk of occupational exposure. The antibody titers of vaccinated patients were assessed by MAT and ELISA. In a second step, vaccinal protection was studied in vivo by checking the seroprotective effect of the human sera injected in an animal model (Meriones unguiculatus) naturally susceptible to the disease. The passive protection was studied by comparing the death rate on five batches of animals to which the bacterium was inoculated. Thus, four batches of animals were injected subcutaneously with a pooled sera of vaccinated people sampled at D0, D15, D135, and D320 after Spirolept vaccination. One control batch was given PBS. One day after injection, the latter batch was inoculated with the homologous strain Verdun of Leptospira interrogans ss icterohemorrhagiae (serogroup Icterohemorrhagiae) used to make the vaccine. RESULTS: The death rate was significantly decreased as soon as D15 after the first injection, even with pooled sera of vaccinated people negative for the MAT. COMMENTS: The Spirolept vaccine induces a protective response against icterohemorrhagiae, which can be transmitted to the animal model and thus is linked to a humoral response.

CLF associates with CLC to form a functional heteromeric ligand for the CNTF receptor complex.

Ciliary neurotrophic factor (CNTF) is a cytokine supporting the differentiation and survival of various cell types in the peripheral and central nervous systems. Its receptor complex consists of a non-signaling alpha chain, CNTFR, and two signaling beta chains, gp130 and the leukemia inhibitory factor receptor (LIFR). Striking phenotypic differences between CNTF- and CNTFR-deficient mice suggest that CNTFR serves as a receptor for a second, developmentally important ligand. We have identified this factor as a stable secreted complex of cardiotrophin-like cytokine (CLC) and the soluble receptor cytokine-like factor-1 (CLF). CLF expression was required for CLC secretion, and the complex acted only on cells expressing functional CNTF receptors. The CLF/CLC complex activated gp130, LIFR and signal transducer and activator of transcription 3 (STAT3) and supported motor neuron survival. Our results indicate that the CLF/CLC complex is a second ligand for CNTFR with potentially important implications in nervous system development.

Total arterial compliance estimated by stroke volume-to-aortic pulse pressure ratio in humans.

On the basis of the windkessel model, the stroke volume-to-aortic pulse pressure ratio (SV/PP) has been proposed as an estimate of total arterial compliance, but recent studies have questioned this approximation. Aortic pressure was obtained at rest in 31 adults undergoing cardiac catheterization (47 +/- 14 yr): controls (n = 7), patients with dilated cardiomyopathy (n = 10), and patients with other cardiac diseases (n = 14). We calculated PP, mean aortic pressure (MAoP), heart period (T), SV (thermodilution cardiac output/heart rate), total peripheral resistance (R), total arterial compliance estimated by area method (Carea), and the time constant of aortic pressure decay in diastole (RCarea). In the overall population (n = 31), there was no significant difference between SV/PP and Carea. SV/PP was linearly related to Carea (SV/PP = 0.99Carea + 0.05; r = 0.98; P < 0.001); the slope and intercept did not differ from unity and zero, respectively. Similar results were obtained in the three subgroups. These results implied that PP/MAoP and T/RCarea were proportionally related (T/RCarea = 1.18PP/MAoP - 0.07; r = 0.96; P < 0.001). We conclude that for humans at rest 1) SV/PP gave a reliable estimate of Carea, and 2) T normalized by the time constant of aortic pressure decay in diastole was proportionally related to PP/MAoP. This last relationship could be considered an aspect of the coupling between the left ventricle and its load.

Sarcomere relaxation in hamster diaphragm muscle.

We characterized instantaneous sarcomere relaxation over the load continuum in isolated hamster diaphragm muscles by means of laser diffraction. In afterloaded twitches, sarcomere relaxation displayed two consecutive phases. The bulk of sarcomere lengthening occurred during the first phase and corresponded in time to muscle lengthening. The second phase of sarcomere relaxation was slower and corresponded in time to tension decay. At initial muscle length, the peak velocity of sarcomere lengthening (SVL) was linearly related to both the maximum extent of sarcomere shortening (delta SL) and sarcomere length at peak shortening (SLmin; each P < 0.01). Varying preload modified the SVL vs. SLmin relationship but not the SVL vs. delta SL relationship. At a given preload, muscle tension decay began at a similar sarcomere length, regardless of the afterload level. In conclusion, our results support the role played by sarcomere length in regulating the diaphragm muscle-lengthening rate but not the rate of tension decline.

Hydroxocobalamin vs cobalt toxicity on rat cardiac and diaphragmatic muscles.

BACKGROUND: Hydroxocobalamin has been shown to be a rapid and powerful antidote in acute cyanide poisoning and to prevent cyanide poisoning during sodium nitroprusside administration. This cobalt-containing compound has been shown to be devoid of significant immediate side effects during acute administration. However, its potential delayed toxicity related to cobalt accumulation in tissue remains unknown. Therefore, we evaluated the toxicity of hydroxocobalamin as compared with that of cobalt salts on rat cardiac and diaphragmatic muscles. METHODS: For a 21-day period, rats were treated intraperitoneally with either hydroxocobalamin (70 mg kg-1 per day, n = 14), cobalt chloride hexahydrate (12 mg kg-1 per day, n = 14) or saline (n = 10). Hydroxocobalamin and cobalt chloride groups received equimolar doses of cobalt. We studied: (1) the mechanical properties of isolated left ventricular papillary muscles and diaphragmatic strips, (2) the cardiac and diaphragmatic cobalt tissue concentrations, and (3) the myocardial histological aspect. RESULTS: During the study period, no significant increase in body weight was noted in the cobalt-treated group (-4 +/- 1%), which was in contrast to the hydroxocobalamin-treated group (+21 +/- 2%) and the saline-treated group (22 +/- 2%). Compared with controls, the mechanical properties of cardiac and diaphragmatic muscles were unchanged after either hydroxocobalamin or cobalt salt treatments, and myocardial histological characteristics were similar in all groups. Conversely, large amounts of cobalt deposit were observed in the cobalt-treated group in both the diaphragm (41.90 +/- 16.30 vs 0.70 +/- 0.40 mu mol mu g-1 in the control group, P < 0.001) and the myocardium (16.90 +/- 6.40 vs 0.14 +/- 0.01 mu mol mu g-1 in the control group, P < 0.001). After hydroxocobalamin administration, cobalt concentrations were significantly lower in the diaphragm (25.10 +/- 16.50 mu mol mu g-1, P < 0.001 vs cobalt-treated group) and the myocardium (4.50 +/- 1.20 mu mol mu g, P < 0.001 vs cobalt-treated group). CONCLUSION: These results indicate that repeated administration of hydroxocobalamin was devoid of significant diaphragmatic and cardiac muscle toxicity and therefore remains a safe antidote for acute cyanide poisoning.

Contraction, relaxation, and economy of force generation in isolated human diaphragm muscle.

Contraction, relaxation, and energetics of normal human diaphragm strips (n = 10) were investigated over the whole load continuum in both twitch and tetanus modes. For a given level of isotonic total force and over a large part of the contraction phase, instantaneous velocity was shown to be a unique function of instantaneous length, regardless of time and initial length. In afterloaded tetanic contractions and over a wide range of loads, the peak lengthening velocity (VL) linearly decreased when maximum extent of muscle shortening (delta L) decreased. Stimulation mode modulated the VL versus delta L relationship, the slope of this linear regression being greater in tetanus than in twitch. Conversely, over a wide range of load, an increase in load linearly accelerated the peak rate of force decay, regardless of the stimulation mode. The energetics of human diaphragm muscle was evaluated in terms of both mechanical activity and economy of force generation. Maximum mechanical work (Wmax) differed significantly according to the stimulation mode, and the relative force at which Wmax occurred was higher in tetanus than in twitch (p < 0.05). The G curvature of the P-V hyperbola and maximum mechanical efficiency were significantly higher in tetanus than in twitch. This strongly suggests that the economy of force generation is higher in tetanus contractions than in twitch.

Influence of dietary polyunsaturated fatty acids on contractility, lusitropy and compliance of isolated rat myocardium.

Two groups of 15 rats were fed for 4 weeks with diets containing 15% by weight of fat varying in polyunsaturated fatty acids (PUFA) content and type. Diet C18:2 (n-6) contained 20% of total fatty acids as linoleic acid and small amount of (n-3) PUFA (0.4% of the total fatty acids). Diet LC (n-3) contained the same amount of 18:2 (n-6) and of long chain (n-3) C20 and C22 PUFA (10% of the total fatty acids). Contents of both saturated fatty acids and amount of total PUFA were kept constant in the two diets. Left ventricular papillary muscle mechanics were studied blind at Lmax and over the entire load-continuum, in terms of inotropy, characteristics of the force-velocity relationship, relaxation and compliance. Inotropy, force-velocity relationships and muscle compliance were similar in both groups. There was a trend towards a lower peak lengthening velocity at preload in the LC (n-3) group (P = 0.10) together with an unchanged peak rate of isometric force decline. This resulted in a significant impairment of the two mechanical indexes testing the load dependence of myocardial relaxation (P = 0.019 and P = 0.002). In conclusion, short-term differences in PUFA regimen were associated with an unchanged myocardial contractility and economy of force generation. The decreased load dependence of relaxation together with unchanged myocardial compliance strongly favored a physiological relevance of the previously reported modifications of sarcoplasmic reticulum phospholipid composition and calcium transport under (n-3) PUFA regimen.

Effects of fatigue on force-velocity relation of diaphragm. Energetic implications.

Characteristics of the force (P)-velocity (V) relationship were investigated before and after fatigue in isolated diaphragm muscle of two species: mouse (n = 12), in which diaphragm is composed almost exclusively of fast-twitch fatigue-resistant fiber type, and rat (n = 12), in which diaphragm contains both fatigue-sensitive and fatigue-resistant fiber types. Following fatigue protocol, the mechanical performance of both the contraction and relaxation phases were significantly depressed in the two species. Consequences of the fatigue procedure on P-V characteristics differed markedly according to the two species. In mouse diaphragm, fatigue trial did not change the G curvature of the P-V hyperbola, the maximum mechanical efficiency Effmax, or the normalized peak power output M2. Conversely, in rat diaphragm, fatigue resulted in higher G curvature (p < 0.001), higher Effmax (p < 0.001) and a lower M2 (p < 0.001) compared with control values. This suggests that fatigue improved the economy of force generation in mixed rat diaphragm and not in mouse. This is consistent with an increased proportion of slow fatigue-resistant fibers caused by fatigue of fast fatigue-sensitive fibers in rat diaphragm.

[Mechanical determinants of isotonic relaxation of the isolated diaphragmatic muscle]. / Déterminants mécaniques de la relaxation isotonique du muscle diaphragmatique isolé.

The aim of this study was to define the mechanical determinants of isotonic relaxation of isolated diaphragm muscle in the rat over a load range (n = 30). We tested several hypotheses to determine the effect of i) load conditions (preload, post-load), ii) sudden changes in load during contraction, iii) length of the muscle at peak shortening, iv) maximal amplitude of shortening (delta L) and v) stimulation conditions on peak rate of isotonic reelongation (+dL/dmax). At tetanus at 30 Hz, +dL/dmax was linearly correlated to delta L peak shortening and total load. Variations in preload, peak shortening or postload did not modify the +dL/dmax vs delta L relationship but such variations did affected the relationships +dL/dmax vs total load or +dL/dmax vs peak shortening. For a given value of L, +dL/dmax was weaker for twitch than for tetanus. In conclusion, four findings show that over a wide lad range the maximal amplitude of shortening the main mechanical determinant of the rate of isotonic reelongation of the isolated diaphragm muscle, independently of the length of the muscle at peak shortening, the initial length of the muscle and independently of the load during reelongation.

Relaxant effects of isoproterenol in isolated cardiac muscle: influence of loading patterns.

The purpose of this study was to test the hypothesis that loading patterns (i.e., loading sequence, total load, and preload) modulate the relaxant effects of isoproterenol. The effects of isoproterenol (10(-6) M) on peak rate of force decline (-dF/dt) were studied in rat left ventricular papillary muscle (n = 24) with respect to two sequences of relaxation: the classical, isotonic-isometric sequence, in which tension fall occurs at initial muscle length, and the physiological, isometric-isotonic sequence, in which tension fall occurs at end-systolic muscle length. The influences of muscle load and initial length were accounted for in the evaluation of relaxation rate by plotting -dF/dt against the entire range of loads both at preload = maximum length (Lmax) and 90% Lmax. The main results are the following: 1) in the classical, isotonic-isometric sequence of relaxation, and whatever the preload, the magnitude of the relaxant effect of isoproterenol increased with load; 2) after reversal into the physiological, isometric-isotonic sequence of relaxation, the relaxant effect of isoproterenol behaved independently of load level in muscle preloaded at Lmax; 3) conversely, in muscle preloaded at 90% Lmax and relaxing according to the physiological sequence, the relaxant effect of isoproterenol increased with load; and 4) the peak relaxant effect of isoproterenol was proportionally higher in the physiological sequence of relaxation than in the classical one and occurred at a similar level of load, whatever the loading sequence and whatever the preload level. Our results indicate that loading patterns finely modulated the relaxant effects of isoproterenol and that muscle length, both before the contraction phase and at the onset of relaxation phase, influenced the effects of isoproterenol on myocardial relaxation rate.

Mechanics of human quadriceps muscle.

Mechanics of human quadriceps muscle strips (vastus lateralis; n = 10) were investigated over the whole load continuum. Mechanical experiments were performed at 29 degrees C and in both twitch and tetanus modes. For a given level of isotonic total load (P) and over a large part of the contraction phase, instantaneous velocity (V) was shown to be a unique function of instantaneous length (L), regardless of time and initial length. By considering this time- and initial length-independent mechanical property between instantaneous L and instantaneous V over the whole P continuum, a three-dimensional P-V-L relationship was constructed. Any variations in stimulation conditions modified the time-independent P-V-L diagram. Such modifications in the P-V-L relationship were characteristics of changes in contractile performance. Moreover, characteristics of the P-V relationship were investigated in both twitch and tetanus modes. The curvature of the P-V hyperbola was significantly higher in tetanus at 30 Hz than in twitch mode (P < 0.001). In conclusion, our study indicates that, in human quadriceps muscles, contractility can be defined as the time- and initial length-invariant part of a three-dimensional P-V-L relationship. Moreover, our data are consistent with an increase in economy of force generation in tetanus contractions compared with that in twitches.

Effects of early and late therapy with perindopril on survival and myocardial inotropic state in experimental dilated cardiomyopathy.

We wished to test (a) whether single-drug therapy with a low dose of the angiotensin-converting enzyme (ACE) inhibitor perindopril has the capacity to improve early survival of the cardiomyopathic Syrian hamster (CSH); (b) whether early treatment with perindopril modifies CSH survival to a greater extent than perindopril treatment initiated later in the course of the disease; and (c) the effects of early and late perindopril therapy on the intrinsic contractility of left ventricular (LV) papillary muscle. We studied CSH from the Bio 53.58 dilated strain (n = 76), in which myocardial necrosis is known to develop from age 30 days, whereas congestive heart failure (CHF) is observed only after age 6 months. Animals were randomly assigned to three groups. In early-treated animals, perindopril (1 mg/kg body weight once daily in distilled water) was administered by force-feeding from age 1 month to 9 months (PE1, n = 21). Animals receiving delayed treatment received distilled water from age 1 month to 6 months, followed by 1 mg/kg body weight from age 6 to 9 months (PE2, n = 34). Controls received distilled water from age 1 month to 9 months (C, n = 21). At endpoint (9 months), mechanical properties of LV papillary muscles and serum ACE activity were studied in a subgroup of 32 CSH (C, n = 8; PE1, n = 10; and PE2, n = 14). Maximum unloaded shortening velocity, maximum extent of systolic shortening in twitch with preload only, and normalized peak of isometric active force were measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Isometric relaxation of isolated diaphragm muscle: influence of load, length, time, and stimulation.

Determinants of the isometric relaxation rate were investigated in isolated rat diaphragm (n = 30). We tested the hypothesis that these determinants could include loading conditions, namely preload and afterload; abrupt changes in load during the contraction phase; stimulation conditions; and time. Two relaxation sequences were studied. When isometric relaxation occurred at initial muscle length (isotonic-isometric sequence), an increase in total load (P) accelerated the negative peak rate of tension decline (-dP/dtmax). Variations in initial length, stimulation, and onset of relaxation did not modify the -dP/dtmax vs. afterload relationship. When isometric relaxation was analyzed after -dP/dtmax, for a given afterload level the instantaneous rate of tension decline (-dP/dt) was a unique function of instantaneous tension, regardless of previous loading conditions, stimulation mode, or time. When the isometric relaxation occurred at end-shortening muscle length (isometric-isotonic sequence), the -dP/dtmax vs. P relationship was flat. The rate of tension decay, as attested by either -dP/dtmax or instantaneous -dP/dt vs. instantaneous tension phase plane, differed markedly depending on stimulation conditions. Thus the regulation of isometric relaxation rate differed according to the relaxation sequence. In muscle isometrically relaxing at initial muscle length, peak isometric relaxation rate was mainly determined by afterload. Conversely, in muscle isometrically relaxing at end-shortening length, isometric relaxation rate was highly dependent on the level of activation and was independent of preload and afterload.

Mechanical determinants of isotonic relaxation in isolated diaphragm muscle.

Determinants of lengthening velocity have not been investigated in the diaphragm muscle. This study was undertaken to define the mechanical determinants of isotonic relaxation rate over the entire load continuum in isolated rat diaphragm (n = 30). We tested the hypothesis that the determinants of lengthening could include loading conditions, namely, preload and afterload; abrupt changes of load during the contraction phase; end-shortening muscle length (ESL); extent of shortening (delta L); time; stimulation mode; and stimulation frequency. In afterloaded contractions preloaded at optimal initial length and stimulated in tetanus at 30 Hz, peak lengthening velocity (+dL/dtmax) was linearly related to delta L, ESL, and/or total load. Varying initial muscle length, ESL, afterload, or the load imposed on the muscle during the isotonic lengthening process did not modify +dL/dtmax vs. delta L relationship, whereas +dL/dtmax vs. load and +dL/dtmax vs. ESL relationships were modified by these procedures. For a given delta L, +dL/dtmax could be modified when lengthening was delayed by reversing the relaxation sequence and when twitch and tetanus modes were compared. In conclusion, our results demonstrate that in isolated diaphragm muscle, delta L is the main determinant of +dL/dtmax over a wide range of loads and under various experimental conditions, independent of ESL and initial muscle length and independent of the load imposed on the muscle during the lengthening process. Time and stimulation mode were also shown to modulate the lengthening rate in diaphragm muscle.

[Role of sarcoplasmic reticulum in the regulation of myocardial relaxation]. / Rôle du réticulum sarcoplasmique dans la régulation de la relaxation myocardique.

In order to investigate cardiac muscle behavior after inhibition of either sarcoplasmic reticulum (SR) Ca2+ release or SR Ca2+ uptake, 35 papillary muscles of adult Wistar rats were studied after a 60 minutes exposure to ryanodine 10(-7) M (n = 11) or to cyclopiazonic acid (CPA) 10(-5) M (n = 14) and compared with a control group containing the solvent alone (n = 10). We measured the maximum extent of muscle shortening of the preloaded twitch (DLp) and the normalized total force of the fully isometric twitch (FTi). The peak lengthening velocity of the preloaded twitch (VRp) and the normalized negative peak force derivative of the fully isometric twitch (-DFi) tested the lusitropic state. Intrinsic changes in the relaxation phase, independent of the contractile state, i.e., the relaxant effects, were analysed using 1) two ratios; the VRp/DLp ratio of the preloaded twitch and the -DFi/FTi ratio of the fully isometric twitch and 2) the slopes of the VR versus DL and of the -DF versus FT relationship over the whole continuum of load. Ryanodine induced a marked negative inotropic effect associated with a decrease in VRp from 2.7 +/- 0.2 to 1.4 +/- 0.2 Lmax/s (p < 0.001). The VRp/DLp ratio and the slope of the VR versus DL relationship remained unchanged, indicating that ryanodine was devoid of intrinsic relaxant effect under isotonic conditions. At a 10/min stimulation frequency, inhibition of Ca(2+)-uptake function of the SR with CPA had no inotropic effect but decreased VRp from 2.9 +/- 0.1 to 2.2 +/- 0.1 Lmax/s (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of cyclopiazonic acid and ryanodine effects on cardiac muscle relaxation.

We investigated cardiac muscle behavior after inhibition of either sarcoplasmic reticulum (SR) Ca2+ release or SR Ca2+ uptake. Mechanics of 35 rat papillary muscles were studied after either ryanodine 10(-7) M (n = 11) or cyclopiazonic acid (CPA) 10(-5) M (n = 14) and compared with a control group containing the solvent alone (n = 10). We measured the maximum extent of shortening (delta L) of the preloaded twitch (delta Lp), and the normalized total force (TF) of the full isometric twitch (TFi). The peak lengthening velocity (Vl) of the preloaded twitch (Vlp) and the normalized negative peak force derivative of the fully isometric twitch (-DFi) tested the lusitropic state. With the influence of shortening and/or load on relaxation taken into account, analysis of relaxation was performed using 1) Vlp-to-delta Lp and magnitude of -DFi-to-TFi ratios and 2) slopes of the Vl-delta L and magnitude of -DF-TF relationships over the entire continuum of load. Ca(2+)-release inhibition with ryanodine induced a negative inotropic effect and a decrease in Vlp from 2.7 +/- 0.2 to 1.4 +/- 0.2 Lmax/S, where Lmax is the initial length at the peak of the length-active tension curve (P < 0.001). The Vlp-to-delta Lp ratio and the slope of the Vl-delta L relationship were preserved, indicating that ryanodine was devoid of intrinsic relaxant effect under isotonic conditions. Ca(2+)-uptake inhibition with CPA had no inotropic effect but decreased Vlp from 2.9 +/- 0.1 to 2.2 +/- 0.1 Lmax/s (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Intrinsic alterations of diaphragm muscle in experimental cardiomyopathy.

Diaphragmatic function was investigated in the cardiomyopathic Syrian hamster (CSH) from the dilated Bio 53:58 strain, after long-term therapy with the angiotensin-converting enzyme inhibitor perindopril. Twenty-two 1-month old CSHs were treated during a 5-month period by either oral gavage with perindopril (1 mg/kg/day) (n = 11) or placebo (n = 11). Control hamsters from the F1B strain received placebo (n = 7). Mechanical properties were studied in isolated diaphragm strips electrically stimulated in both twitch and tetanic conditions. Compared with F1B control hamsters, peak active tension and positive (+dP/dtmax) and negative (-dP/dtmax) peaks of isometric tension derivative were significantly depressed in placebo treated CSHs. Compared with placebo-treated CSHs, peak active tension was significantly higher in perindopril-treated CSHs in both twitch (25 +/- 4 vs 16 +/- 1 mN/mm2; p < 0.01) and tetanus modes (56 +/- 4 vs 38 +/- 2 mN/mm2; p < 0.01). Moreover, +dP/dtmax and -dP/dtmax were improved significantly in twitch (p < 0.01 and p < 0.01, respectively) and tetanus modes (p < 0.05 and p < 0.01, respectively). We conclude that, in the CSH, long-term therapy with the angiotensin-converting enzyme inhibitor perindopril helped to preserve the diaphragmatic function.

Comparative migration and development of astroglial and oligodendroglial cell populations from a brain xenograft.

In previous studies of brain transplantation, the fate of the implanted glial cells has been investigated separately; that is, the interest has been focused either on the astroglia or on the oligodendroglia. However, the two populations of implanted glial cells may interact with each other, for example by secreting species-specific factors or by inducing reactions by the host. We have used two different models of brain transplantation: one that allows the identification of the implanted astrocytes, and another that allows the identification of the implanted oligodendroglia. The present model is a combination of both; it consists of the grafting of embryonic rabbit brain fragments into the brains of neonatal Shiverer mice. The myelin made by the implanted oligodendrocytes is identified by anti-myelin basic protein immunohistochemistry. The implanted astrocytes are identified by a monoclonal antibody that combines with rabbit but not with mouse glial fibrillary acidic protein. This study shows that although they use the same major routes of migration, both populations of glial cells tend to move differently. They demonstrate areas of common settlement but also areas where only one population of implanted glia is present. From the site of implantation in the dorsal striatum, the major routes of migration are the corpus callosum, the white matter fascicles in the striatum, and the internal capsule. After a delay of 6 weeks, no significant prevalence of one population of implanted glial cells over the other was observed.

In situ transformation of striatal glia into cerebellar-like glia after brain transplantation.

Transplants of striatum from rabbit embryo were implanted into the colliculus posterior of newborn mice. After 4 weeks, astroglial cells derived from the transplant had migrated into the cerebellum of the host. Whenever they had settled in the cerebellum they presented forms similar to local glia. Some migrated glial cells were found to transform into forms of glia, such as radial-like glia, which are not present in the striatum. This observation confirms that glial precursor cells are highly plastic. It is an in vivo demonstration that local conditions alone define the morphology of glial cells. After grafting in an heterotopic location they take on forms that they were not destined to express in the region of origin.

Migration patterns of donor astrocytes after reciprocal striatum-cerebellum transplantation into newborn hosts.

Fragments of striatum or cerebellum from E 25 rabbit embryo were implanted into either the striatum or the mesencephalon of newborn mice. Implanted rabbit astrocytes were selectively identified by monoclonal antibodies to the GFAP which are unable to combine with mouse GFAP. Previous investigations had shown that xenogenic astrocytes have the capacity to migrate in host CNS. The purpose of this study was to compare the patterns of migration of transplant-derived astroglial cells according to the topographic origin of the transplant and location of the grafting site. We found that the migration pattern of the grafted cells from any of both selected sites of implantation was independent from the topographic origin of the transplant. The routes as well as the distances of migration were similar after homo- or heterotopic transplantation. We conclude that astroglial cells or their precursors do not express information which would direct them to move specifically toward a defined region in the host brain according to the region of origin in the donor.