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Biomedical subjects

M Hultcrantz

Publications and source records attributed to M Hultcrantz.

At least 55 records · Page 3Linked to original sources

Inner ear morphology in CBA/Ca and C57BL/6J mice in relationship to noise, age and phenotype.

CBA/Ca mice showing moderate hearing losses with onset late in life and C57BL/6J mice with progressive hearing losses starting when animals were young adults were exposed to a 2-7 kHz, 120 dB SPL noise band for 5 min in order to investigate morphological consequences to noise as a function of age and genotype. Permanent threshold shifts were determined by auditory brainstem responses 1 month after noise exposure at 1, 3 and 6 months of age. CBA mice had a decreasing susceptibility to noise with increasing age, while C57 mice remained equally susceptible throughout all ages tested. The threshold shifts were then analyzed in relation to morphological changes of the organ of Corti as visualized by light microscopy (LM), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). CBA mice exposed at 1 month and sacrificed at 2 months had seemingly normal cochlear morphologies under LM. In these animals SEM findings demonstrated mild stereocilia damage to noise trauma, but not when mice were exposed at 3 and 6 months. There was no visible morphological aging of hair cells found during the period tested. In contrast, the C57 mice had early hair cell changes including bent and fused stereocilia, bulging of the cuticular plates, hair cell loss and swelling of afferent dendrites. These changes became more pronounced throughout the test periods with the variability of damage in this strain more evident over time. This pattern was also aggravated in all C57 age groups tested after noise exposure. Quantification with cytocochleograms demonstrated a statistically different reaction pattern to noise trauma between the two different genotypes of mice.

Aging↗

Expression of glycoconjugates in the mouse inner ear after prenatal irradiation.

Irradiation of the murine fetal inner ear is known to produce damage both to the vestibular and cochlear parts in the adult mouse. Fluorescein-labelled lectins were used to reveal possible differences in the glycoconjugate content between normal and irradiated inner ears. In the vestibular part, the otoconia showed the highest uptake of labelled sugars. This uptake was weaker after irradiation when compared to non-irradiated specimens. The type I hair cells in the ampulla and in the utricle showed a weaker uptake, but no labelling was demonstrated in the type II hair cells compared to the non-irradiated controls. In the cochlear part of the inner ear almost no uptake of fluorescent-binding lectins could be demonstrated in the irradiated groups except for in the tectorial membrane. In the endolymphatic sac no uptake was shown after prenatal irradiation. These findings are discussed and correlated to the already known damage of the inner ear following prenatal irradiation.

Animals↗

Stage dependent development of intraocular cochlear grafts.

The intraocular grafting technique was employed to test whether the peripheral hearing organ, the cochlea, is capable of survival and an organized development in total isolation from the temporal bone. Rat cochleae obtained from gestation day 16, postnatal day 1 and 7 were chosen for transplantation into the anterior chamber of the eye of adult Sprague-Dawley rats. The grafts were maintained in the anterior chamber for 6, 10, or 15 weeks survival time. The salient features of this study is that 1) cochlear structures survive and, 2) the cochlear structures develop beyond their pre-grafted stage as determined from light and electron micrographs. In the present study, the grafts obtained at gestation day 16 (GD 16) and postnatal day 1 gave a much higher rate of survival and development than the postnatal day 7 grafts. In addition, grafts maintained for either 6 or 10 weeks had a better survival rate than those grafts left for 15 weeks. It is estimated from light and electron micrographs that the gestation day 16 otocysts that were maintained for 10 weeks, developed to the equivalent of a postnatal day 10 cochlea. The grafts obtained from postnatal day one rats developed to the equivalent of approximately 14 days after birth. Interestingly, in the absence of synaptic contact, the inner and outer hair cells were capable of survival, differentiation and maturation. It remains to be determined if the spiral ganglion cells require additional neurotrophic factors for survival in the anterior chamber of the eye.

Animals↗

Effects of neonatal deafening and chronic intracochlear electrical stimulation on the cochlear nucleus in cats.

Four newborn kittens were deafened by daily intramuscular injections of neomycin sulfate, beginning the day after birth and continuing for 14-16 days. At 10-16 weeks of age the deaf kittens were implanted unilaterally with a four wire intracochlear electrode array. The animals were stimulated daily (starting at 13-18 weeks of age), for a period of one hour, at 6 dB above the electrically evoked auditory brainstem response threshold. After 3 months of chronic intracochlear electrical stimulation, animals were studied in acute electrophysiological experiments and euthanized for histological studies. This study compares the stimulated and control cochlear nuclei (CN) of these deafened animals to the CN of four normal adult cats. Statistical comparisons of spherical cell densities in the anteroventral cochlear nucleus (AVCN), cross-sectional spherical cell areas, and volumes of the cochlear nucleus subdivisions were included in the analysis. The results indicate that, by all of these measures, the cochlear nuclei in neonatally deafened animals were significantly different from the cochlear nuclei of control animals. As a result of deafening, the density of spherical cells was decreased by 30%, the cross-sectional areas of spherical cells were reduced by 20%, and the volume of the cochlear nucleus was reduced by 25%. These changes were observed in both cochlear nuclei (ipsilateral to both stimulated and unstimulated ears) of the deafened animals. With the measures employed, no significant difference was demonstrated in comparisons between the deafened/unstimulated and the deafened/stimulated cochlear nuclei. That is, no reversal of the profound effects of deafening was observed in the cochlear nuclei as a consequence of chronic intracochlear electrical stimulation which was begun 11 to 16 weeks after deafening.

Animals↗

Vascular supply of the endolymphatic sac. A gross and ultrastructural study in the Mongolian gerbil under normal and experimental conditions.

The vascular network of the gerbilline endolymphatic sac (ES) and its dynamics were studied using different morphological procedures. The normal condition was compared to serum osmotic alterations induced by changing the daily water intake of the animals. The gross morphology was studied after intracardiac injection of Berlin Blue, while light (LM) and transmission electron microscopy (TEM) were applied for the ultrastructural analysis. A rich vascular supply was seen in the intermediate portion of the normal ES, and the presence of micropores and fenestrations confirmed also in this animal species the importance of this region for fluid exchange. The lacunar arrangement of the vessels in the distal portion of the ES, together with the close vicinity of this area to the bone marrow, led to the hypothesis that the distal ES possesses a functional role as blood reservoir. The hyperosmotic condition induced by water deprivation appeared to affect mostly the morphology of the red cells. In some of the capillaries, a thrombus-like occlusion was also evident. This vascular occlusive condition appeared to be partly reversible when water intake was reestablished, although the morphological alterations induced by the hyperosmotic condition to the subepithelial tissue appeared not to be reversible.

Animals↗

Endolymphatic sac morphology following long-term kanamycin intoxication.

The well-known toxicity pattern of aminoglycoside antibiotics has been used with the aim to produce waste products in the inner ear. The endolymphatic sac was studied after daily intraperitoneal injection of 75 mg/kg kanamycin for 10 and 20 days to see whether or not the endolymphatic sac showed signs of increased phagocytic activity. The epithelium of the endolymphatic sac was reduced in height, the cells were swollen and extremely thin. The dark epithelial cells were outnumbering the light cells. The subepithelial tissue showed an edematous swelling containing few blood vessels, collagen fibrils and fibroblasts with an empty appearance. There were few wide lateral intercellular spaces and there were intraluminal free floating cells. There were, in all, no clear morphological signs of increased phagocytic activity in the epithelium of the endolymphatic sac.

Animals↗

Embryonic and postnatal development of endolymphatic sac blood vessels.

The development of perisaccular blood vessels is described during embryology and the postnatal period of the mouse. Primitive sinusoidal vessels already appear at the early otocyst stage as the future endolymphatic sac is formed. Before birth the vasculature attains a more mature appearance with tubular, somewhat fully developed blood vessels. At this stage a primitive basement membrane is also formed. Soon after birth the blood vessels appear mature with developed fenestrations and micropores, giving them an appearance comparable to blood vessels in other fluid transporting organs.

Animals↗

Correlation between auditory brainstem recordings and morphology as seen through the scanning electron microscope.

Pregnant CBA/CBA mice were exposed to 0.5, 1 and 2 Grey (Gy), (1 Gy = 100 rad) in single doses with whole body gamma-irradiation on the 12th, 13th and 16th gestational days, respectively. The animals were tested at an age of one month for vestibular and cochlear function. Thereafter the inner ears were analyzed with scanning electron microscopy. A morphological analysis with cytocochleograms was performed. Morphological changes in the vestibular part showed gross malformations in the cristae ampullares. Hair cells of type I seemed to be more severely changed than hair cells type II. The macula utriculi also showed malformations of the otoconia. All these changes were more pronounced when the irradiation was given early during pregnancy and with the highest doses used, except the otoconia which were more injured when irradiated day 16 of gestation. No disturbances of the equilibrium reflexes were noted. In the cochlea a dose-dependent, time-related damage pattern was demonstrated with pathological changes of outer (OHC) and inner (IHC) hair cells. When tested electrophysiologically for auditory function with auditory brainstem recordings (ABR), elevated thresholds were revealed different in shape depending on when during pregnancy irradiation took place. A good correlation existed between the morphological changes as seen in the cytocochleograms and the functional changes documented with the ABR.

Aging↗

A scanning electron microscopic study of vestibular organ malformation following prenatal gamma irradiation.

Pregnant CBA/CBA mice were exposed to 1 and 2 Gy whole-body gamma irradiation on the 13th and 16th gestational days, respectively. The litters were born on the 21st day of gestation and were tested for vestibular function at the age of 1 month. The animals were then sacrificed and their inner ears were analyzed by scanning electron microscopy. No disturbances of vestibular function were noted in the animals studied. However, the cristae ampullares showed severe malformations as regards their gross shape, with irregularities of their outer contours. Type I hair cells seemed to be more severely changed than Type II hair cells, with fusion of sensory hairs, giant hair formation and bulging of the cuticular plate. In certain sites the hair cells were totally missing. These derangements were usually located in the central areas of the cristae ampullares and in the striolar portion of the maculae utriculi. The morphological damage found showed a dose-dependent, time-related pattern.

Abnormalities, Radiation-Induced↗

Morphological and electrophysiological study of the inner ear and the central auditory pathways following whole body fetal irradiation.

Pregnant CBA/CBA mice were whole body irradiated with 2 Gy on the 13th or 16th day of gestation, respectively. The exposed fetuses were raised to an age of 21 postnatal days. Auditory brainstem recordings of threshold levels showed a considerable elevation independent of if irradiation had been performed on either the 13th gestational day or the 16th gestational day. In exposed animals a latency difference occurs in the peaks that increases from peak 1 to peak 5, measuring in peak 5 up to 1.16 ms. Also the peak-to-peak length of waves 1-5 increases in irradiated animals. Scanning electron microscopy of the cochleae showed varying degrees of stereociliary derangement of both outer and inner hair cells, particularly in cochleae where irradiation had been performed on the 13th gestational day, but not loss of hair cells. Light microscopic analysis of auditory brainstem nuclei revealed normal conditions except that in inner ears exposed on the 16th gestational day the flocculus was fused to the lateral surface of the anterior ventral cochlear nucleus. It is concluded that the elevated threshold levels in irradiated animals are most likely due to pathological changes in the peripheral receptor organ whereas the increased latencies and the increased peak-to-peak length likewise reflect functional changes in the brainstem auditory nuclei.

Animals↗

Structure and function of the adult cochlea following prenatal irradiation.

The structure and function of the cochlea of the CBA/CBA mouse were analysed after exposure to single doses of gamma irradiation during embryonic development. Pregnant mice were exposed to 0.5, 1 and 2 Gy, respectively, on either the 12th, 13th, or 16th gestational day. Morphological analyses were performed using light microscopy, scanning electron microscopy and transmission electron microscopy while the function was measured with the auditory brainstem response (ABR) technique. The inner and outer hair cells showed pathological changes of sensory hairs and their anchoring in the cuticular plate. Cytocochleogram counting was performed classifying the morphological changes into three different severity degrees of pathology. A dose dependent pattern of irradiation induced pathology was documented. A threshold shift of about 20 dB was found after irradiation with 2 Gy. A flat loss of ABR curves occurred in animals irradiated on the 12th or 16th gestational days. If the fetuses were exposed on the 13th gestational day the high frequencies resulted in more pronounced damage than the middle and low frequencies.

Animals↗

Structure and function of the adult inner ear in the mouse following prenatal irradiation.

The function and morphology of the vestibular and cochlear parts of the inner ear have been examined after prenatal irradiation on the 12th, 13th and 16th gestational days in the CBA/CBA mouse. Irradiation was performed with a 0.5, 1 or 2 Gy single dose, whole body irradiation of the pregnant female. The irradiated fetuses were born after full term pregnancies and reached maturity (were 1--2 months old) before inner ears were analyzed with regard to vestibular tests, auditory thresholds and morphology. Morphology was studied by light microscopy (LM), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Auditory function was analyzed by frequency specific auditory brainstem response (ABR). Irradiation doses exceeding 2 Gy caused death to the pregnant female, abortion or malformed litters which were eaten by their mothers. Doses of 0.5, 1 and 2 Gy caused malformed cristae ampullares and maculae utriculi, in particular after exposure on the 12th or 13th gestational days. After those doses no abnormality of clinical behaviour of the animals was found. Ultrastructurally, type I hair cells (HC) of the vestibular part seemed more vulnerable to irradiation than the type II HC while the outer (OHC) and inner (IHC) hair cells appeared equally vulnerable. The ultrastructural changes of hair cells were predominantly localized to the hair cell surface showing a defect cuticle which was sometimes malformed and bulging. Sensory hair fusion occurred with a resulting poor maturation of sensory hair rootlets. The efferent nerve endings were estimated to be reduced in number but, if present, they had a normal ultrastructure. Otoconia showed severe morphological damage following irradiation particularly if exposed on the 16th gestational day. Malformed and fused otoconia were frequent having a disarrayed matrix. The irradiation induced morphological alterations in vivo could be reproduced in the in vitro systems. In addition, a retarded growth of the in vitro developing inner ear anlage was estimated to be the same for the vestibular and cochlear parts. The cochlear part of the inner ear showed a dose and age dependent hearing loss following irradiation. A shift of the ABR threshold was recorded in all exposed groups that were irradiated with 2 Gy. A correlation was found between the individual ABR-audiograms and the degree of morphological HC damage in the cochlea along the basilar membrane. The 12th gestational day inner ear anlage was most vulnerable to irradiation. The 13th gestational day inner ear was almost equally vulnerable and showed a dose-response relationship.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Turnover of sulphated macromolecules in the murine endolymphatic sac after long-term kanamycin treatment.

Radioactively labeled sulphur was injected into 12 mice of the NMRI strain 20 days after pretreatment with kanamycin. The animals were decapitated after intervals ranging from 2 minutes to 24 hours after injection. After a routine autoradiographic procedure, darkly stained silver grains were detected in the endolymphatic sac (ES) and its surroundings. One hour after injection, the grains were found in the surrounding blood vessels. Eleven hours later, maximal uptake was seen in the epithelial cells of the ES in the kanamycin-treated animals. Twenty-four hours after injection, a faint S35 uptake in the ES could still be detected. An increase in the ES activity, indicated by an increased number of free-floating cells and the secretion of a sulphur-containing intraluminal substance, did not occur. The spreading pattern of sulphur, as shown in this investigation, does not support the theory that waste products from the inner ear, transported to the ES by the longitudinal flow, produces an increased activity in the sac after long pretreatment with kanamycin. In 12 control animals, no difference in the distribution of labeling was observed, but there was an additional uptake in the free intraluminal cells which was not seen in the kanamycin group.

Animals↗

Influence of gamma irradiation on developing otoconia.

Thirty-two CBA/CBA mice were irradiated in utero on the 12th, 13th, or 16th gestational day with doses of 0.5, 1, and 2 Gy, respectively (1 Gy = 100 rads). One month after birth, the inner ears were examined by light microscopy and transmission and scanning electron microscopy. Otoconia with defective shapes was identified frequently. The strict hexagonal shape of normal otoconia seldom developed and, in exposed animals, had often been replaced with rounded, oval, or elongated shapes. The otoconial substructure was disarrayed, and fusion of two or three otoconia occurred. Degenerating otoconia appeared in the intercellular space of the dark-cell epithelium. Fetal gross structures of otoconia persisted into maturity.

Animals↗

Age-related degeneration of the organ of Corti in two genotypes of mice.

Degenerative changes in the organ of Corti were investigated in two genotypes of mice, CBA/Ca (moderate age-related late-onset hearing loss) and C57BL/6J (spontaneous early-onset auditory deterioration), ranging in age from 1 to 21 months (C57BL) and from 1 to 33 months (CBA). Light, transmission and scanning electron microscopies were used for qualitative and quantitative analyses. Alterations of deterioration in the CBA-mouse cochlea showed a late-onset loss of hair cells, lipofuscin in the outer hair cells (OHCs), giant stereocilia on the inner hair cells and elevated pillar heads. In C57BL mice, the primary lesions of the organ of Corti include early damage of stereocilia on OHCs, missing OHCs, and a ruptured reticular lamina. Giant cilia and elevated pillar heads were not evident in C57BL mice. In the aged C57BL mouse cochlea, the whole organ of Corti was collapsed and replaced by the supporting cells, whilst in the oldest CBA mice, completely normal-looking OHCs still remained even in severely deteriorated areas of the organ of Corti. The results indicate that the patterns of degeneration of the organ of Corti are different between CBA/Ca and C57BL/6J mice, probably under the control of different genes.

Aging↗

Degeneration patterns of actin distribution in the organ of corti in two genotypes of mice.

Alterations of the auditory system during ageing and after noise damage have been studied earlier in two genotypes of mice, CBA/Ca and C57BL/6J, the former of which shows a late-onset hearing loss and the latter a high susceptibility to ageing and acoustic trauma early in life. The two strains display similarities to the different types of human age-related hearing loss. In the present study, the different patterns of hair cell degeneration were visualized by phalloidin-labelled actin in the two strains of mice with increasing age. At 1 month of age there were no major differences in the actin distribution between the two genotypes. With increasing age, CBA mice retained a regular pattern of actin content in the cuticular plate but some hair cells were missing. In contrast, the C57BL mice showed a severely distorted architecture of the cutis plate (CP) with less actin labelling, missing hair cells and scar formation. The instability of actin in the hair cells of C57BL mice might result in their high susceptibility to ageing and noise damage.

Actins↗

Congenital malformation of the inner ear and recurrent meningitis. A case report.

Congenital deformities of the inner ear can be associated with meningitis and varying degrees of hearing loss or deafness. Recurrent periods of meningitis, sometimes lethal, are due to communication between the middle ear cavity and the subarachnoid space. Different types of congenital dysplasia have been classified earlier and we report a 3-year-old girl with unilateral deafness, episodes of meningitis and a malformation of the inner ear and the footplate of the stapes.

Child, Preschool↗