© 1991 Karger AG. Basel 0001-5180/91/1404-0369 $ 2.75/0
Acia Anat 1991;140:369-372
Adrenergic Nerve Fibers in the Human Fetal Sciatic Nerve1 ./. Koistinaho Laboratory of Gerontology. Department of Public Health. University of Tampere, Finland
KeyWords. Human • Sciatic nerve • Adrenergic • Neuropeptide Y • Endoneurium • Epiperineurium • Development
Introduction The peripheral nerve receives adrenergic innervation [Appenzeller et al.. 1984; Dhital et al., 1985; Rechthand et al., 1986; Koistinaho et al., 1989]. A dense adrenergic network has been found around epiperineurial arterioles in the sciatic and vagal nerves of the rat and rabbit. Single adrenergic nerve fibers have also been observed in the endoneurium, occasionally contacting capillaries | Recht hand et al., 1986; Koistinaho et al.. 1989]. In addition, serotonin | Appenzeller et al.. 1984] and some neuropep tides. e.g. substance P, vasoactive intestinal peptide [Appenzeller et al., 1984]. neuropeptide Y (NPY) and calcitonin-gene-related peptide [Dhital and Appenzeller. 1 This study was financially supported by the Finnish Cultural Foun dation of Pirkanmaa.
1988], are neurotransmitters found in association with blood vessels in the epiperineurium of the rat. guinea pig or rabbit peripheral nerves. Although the perivascular innervation in the epiperi neurium and endoneurium of the peripheral nerve is rel atively well described in rodents and the monkey [Hara and Kobayashi. 1987]. there has been limited investiga tions of the perivascular innervation in the human periph eral nerve. Using electron microscopy, Grover-Johnson et al. [ 1981 ] found perivascular nerve profiles around epineurial arterioles in the human sural nerve. They also reported that the number of perivascular axons was decreased in the epincurium of the diabetic sural nerve. However, there have been no studies exploring the trans mitter nature of the innervation of the microvessels in the human peripheral nerve, or aiming to determine whether adrenergic nerve fibers also exist in the endoneurium.
Downloaded by: Temple University 155.247.166.234 - 1/7/2020 10:56:08 AM
Abstract. The adrenergic ¡nervation was studied in the human sciatic nerve at the gestational age of 16. 17.18 and 21 weeks. Formaldehyde-induced catecholamine fluorescence, tyrosine hydroxylase (TII) and neuropeptide Y (NPY) peroxidase-antiperoxidase immunohistochemistry methods were used. At the gestational age of 16.17 and 18 weeks no adrenergic or NPY-positive nerve fibers were seen. At 21 weeks both fluorescence microscopy and TH irnmunohistochcmistry showed adrenergic nerve fibers around arterioles in the epiperineurium and single nerve fibers in the endoneurium not related to blood vessels. The number of adrenergic nerve fibers appeared to be higher in the sciatic than in the tibial segment of the nerve. At this age, as at earlier stages of gestation, no NPY-positive nerve fibers were seen either in the epiperineurium or in the endoneurium. The results suggest that adrenergic nerve fibers may be associated with the epiperineurial blood vessels in the human sciatic nerve, and that the innervation starts to develop between 18 and 21 weeks of gestational age.
370
Therefore, it was interesting to study the adrenergic and NPY-ergic innervation in the human fetal sciatic and tibia! nerves.
Material and Methods Normal human fetuses were received from legal interruptions of pregnancy. The gestational age of the fetuses ranged from 16 to 21 weeks. A total of 12 sciatic nerves were studied. Within 3 h of delivery, the nerves were dissected out and immersed either in liquid nitrogen or in 4% formaldehyde. The frozen samples were freeze-dried and pro cessed according to the formaldehyde-induced fluorescence method [Koistinaho et al.. 1989]. The formaldehyde-fixed samples were pro cessed according to the original peroxidase-antiperoxidase immunohistochemistry technique [Sternbcrgcr. 1979| using tyrosine hydroxy lase (TH) (EugeneTechnics. Allendale. N.J.. USA)and NPY (Milab. Sweden) antibodies, diluted 1:100 and 1:300. respectively. The sec tions were viewed using an Olympus Vanox T light and fluorescence microscope.
Results In the sciatic nerves from fetuses at 19 weeks of gesta tional age and younger, no adrenergic nerve fibers were seen by fluorescence microscopy. TH and NPY immunohistochemistry also gave negative results. In the sciatic nerve from the fetuses at 21 weeks of ges tational age, fluorescence microscopy showed adrenergic nerve fibers both in the epiperineurium and in the endoncurium (fig. 1-3). The number of nerve fibers appeared to be higher in the proximal than in the distal part of the nerve. In the epiperineurium. adrenergic nerve fibers were always associated with arterioles or arteries of varyingsize. In the cndoncurium. adrenergic nerve fibers were usually not found contacting blood vessels. TH-like immunoreactivity corresponded to the adren ergic nerve fibers seen in fluorescence microscopy, but the intensity of the staining varied and was weaker in the endoneurium than in the epiperineurium (fig.4). On the other hand. NPY-likc immunoreactivity was found nei ther in the perivascular nerve fibers, nor in the epiperi neurium. nor in the endoneurium.
Discusssion Perivascular adrenergic nerve fibers in the human sci atic nerve were observed first in 21-week-old fetuses. In previous studies on human fetuses, fluorescent adrener gic nerve fibers were first observed in the gut at 10 weeks
|Rcad and Burnstock, 1970], in the eye at 8-10 weeks [Ehingcr and Sjoberg, 1971], in the heart at 16-18 weeks |K anervaet al.. 1974] and in the pial vessels at 15 weeks [Nobin and Bjorklund. 1973] of gestational age. Our results are in agreement with the suggestion that, in humans, the development of adrenergic innervation is slower in the cardiovascular system than in other organs, e.g. in the gastrointestinal tract [Kanerva et al.. 1974]. In the human sural nerve, blood vessels are absent up to 17 weeks of gestational age, and are first observed 1 week later in the epiperineurium [Ochoa. 1971]. Since adrenergic nerve fibers are associated with the arterioles and arteries in the epiperineurium of human and rodent peripheral nerves [Grover-Johnson et al.. 1981; Rechthand et al.. 1986: Koistinaho et al.. 1989], the appearance of blood vessels in the fetal nerve may be required before adrenergic nerve fibers are able to grow in the epiperineurium. Stimulation of lumbar sympathetic ganglia reduces nerve blood flow, constricts epiperineurial blood vessels and closes endoncurial capillaries in the rabbit sciatic nerve [Lundborg. 1970; Selanderet al.. 1985]. indicating that adrenergic nerve fibers play an important role in con trolling blood flow in the normal peripheral nerve. As adrenergic nerve fibers were present in the epiperineu rium and endoneurium in the sciatic nerve of a 2 1-weekold fetus, it is likely that adrenergic nerve fibers also have a role in controlling blood flow in human nerves. Since synapses are usually found 2-3 weeks after nerve fibers have developed in the human autonomic nervous system |Kanerva et al., 1974]. adrenergic nerve fibers in the human sciatic nerve may become functional as early as at 23-25 weeks of gestational age. TH immunohistochemistry has been used as a marker for adrenergic neurons and nerve fibers in adult and fetal tissues [H ervonenetal., in press; Jarvi. 1989]. Inthe pres ent study, only a few faint TH-immunoreactive nerve fibers were seen in the sciatic nerve of 21-week-old fe tuses. As catecholamines may not be liberated from nerve fibers at this stage of development, the amount and activ ity of TH arc probably very low in adrenergic nerve fibers due to low synthesis of noradrenaline. Similarly, unde tectable NPY-containing nerve fibers, which in adults may have a strong vasoconstrictive effect [Edvinsson et al.. 1987], may be explained by the immaturity of the autonomic nervous system at the age of 21 weeks in the human fetus. The number of adrenergic nerve fibers was higher in the proximal part than in the distal part of the sciatic nerve in the 21-week-old fetuses, and adrenergic nerve fibers
Downloaded by: Temple University 155.247.166.234 - 1/7/2020 10:56:08 AM
Koistinaho
Adrenergic Nerve Fibers in the Human Fetal Sciatic Nerve
371
were also found in the endoneurium not related to blood vessels. Previous studies on the peripheral nerves of the adult rat and rabbit have shown a similar distribution of adrenergic nerve fibers in the epiperineurium and endoneurium |Appenzeller et al.. 1984; Rechthand et al., 1986; Koistinaho et al.. 1989]. There is also evidence that adrenergic innervation in the peripheral nerve is altered both in experimental and human diabetes [Grover-John-
son et al.. 1981; Dhital et al.. 1985; Koistinaho et al., 1990b] and also during aging | Koistinaho et al., 1990a] and in chronic hypertension in the rat (Koistinaho et al.. 1989], Although the present study used fetal tissue, it is suggested on the basis of the similar distribution of adrenergic innerva tion in the human and rodent sciatic nerve that the rodent sciatic nerve could serve as a model in studying the peri vascular innervation in peripheral neuropathies.
Downloaded by: Temple University 155.247.166.234 - 1/7/2020 10:56:08 AM
Fig. 1-3. Fluorescence micro graphs showing adrenergic nerve fibers in the epineurium (black arrows) and in the endoneuriunt (open arrows). The nerve fibers in the epineurium arc usually associ ated with blood vessels. 1, 2 x6()(). 3 x 300. Fig. 4. Micrograph showing TIIimmunoreactive nerve fibers (black arrows) in the endoneurium. X 600.
372
Koistinaho
Appenzeller, O.: Dhital. K.K:. Cowen.T.: Burnstock, G.: The nerves to blood vessels supplying blood to nerves: the innervation of vasa nervorum. Brain Res. 304: 383-386 (1984). Dhital. K.K.: Appenzeller. O.: Innervation of vasa nervorum; in Burnstock. Griffith. Nonadrcnergic innervation of blood vessels, pp. 191-211 (CRC Press. Boca Raton 1988). Dhital. K.: Lincoln. J.: Appenzeller. O.: Burnstock. G.: Adrenergic innervation of vasa and nervi nervorum of optic, sciatic, vagus and sympathetic nerve trunk in normal and streptozotocin-diabetic rats. Brain Res. 367: 36—14 (1985). .Edvinsson. L.: MacKenzie. E.T.; McCulloh. J.; Uddman. R.: Perivas cular innervation and receptor mechanisms in cerebrovascular bed: in Day, White. Cerebral blood flow: physiological and clinical aspects, pp. 145-172 (McGraw-Hill. New York 1987). Ehingcr. B.: Sjoberg. N.-O.: Development of the ocular adrenergic nerve supply in man and guinea-pig. Z. Zellforsch 188: 579-592 (1971). Grover-Johnson.N.M.: Baumann. F.G.: Imparato. A.M.: Kim. G.E.; Thomas. P.K.: Abnormal innervation of lower limb cpiiicurial arterioles in human diabetes. Diabetologia 20: 31-38 (1981). Hara. H.: Kobayashi. S.: Adrenergic innervation of the vasa nervorum in the cranial nerves and spinal roots in the subarachnoid space. Exp. Neurol. 98: 673-676 (1987). Ilervonen. A.: Pelto-Huikko. M.: Pickel. V.M.; Reis. D J .: Joh.T.lL: Immunohistochemical localization of the catecholamine synthe sizing enzymes and enkephalin-like immunoreactivity in the human fetal adrenal medulla. Anat. Embryol. (in press). Järvi. R.: Localization of bombesin-, neuropeptide Y-. enkephalinand tyrosine hvdroxylase-like immunoreaetivities in rat coeliacsuperior mesenteric ganglion. Histochemistry 92: 231-236 (1989). Kanerva. L.: Hervonen. A.: I lervonen, H.: Morphological character istics of the ontogenesis of the mammalian peripheral adrenergic nervous system with special remarks on the human fetus. Med. Biol. 52: 144-153 (1974). Koistinaho. J.: Wadhwani. K.C.; Rapoport. S.L: Increased density of adrenergic innervation in the tibial and vagus nerves of sponta neously hypertensive rats. J. Neurosci. Res. 24: 424—43(1 (1989).
Koistinaho. J.; Wadhwani. K.C.: Rapoport. S.L: Adrenergic innerva tion of the tibial and vagus nerves in rats of different ages. Mech. Ageing Dev. 52: 195-205 (1990a). Koistinaho. J.; Wadhwani. K.C.; Rapoport. S.L: Adrenergic innerva tion in the tibial and vagus nerves of rats with strcptozotocininduced diabetes. Brain Res. 513: 106-112 (1990b). Lundborg, G.: Ischemic nerve injury. Scand J plast. Reconstr. Surg.. suppl. 6. pp. 1—46 (1970). Nobin. A.; Bjbrklund. A.: Topography of the monoamine neuron sys tems in the human brain as revealed in fetuses. Acta physiol, scand.. suppl. 388 (1973). Ochoa. J.: The sural nerve of the human foetus: electron microscope observations and counts of axons. J. Anat. 108: 231-245 (1971). Read, J.R.; Burnstock, Ci.: Development of the adrenergic innerva tion and chromaffin cells in the human fetal gut. Dev. Biol. 22: 513-534(1970). Rechthand, E.: Hervonen. A.; Sato. S.: Rapoport. S.L: Distribution of adrenergic innervation of blood vessels in peripheral nerve. Brain Res. 374: 185-189(1986). Selander. D.: Mansson. L.G.: Karlsson. L.: Svanvik. J.: Adrenergic vasoconstriction in peripheral nerves of the rabbit. Anaesthesiol ogy 62: 6-10 (1985). Sternbergcr. L.A.: Immunohistochemistry; 2nd ed. (Wiley. New York 1979).
Received: October 25. 1990 Accepted: December 20. 1990 Dr. J. Koistinaho Laboratory of Gerontology Department of Public Health University of Tampere PO Box 607 SF-33101 Tampere (Finland)
Downloaded by: Temple University 155.247.166.234 - 1/7/2020 10:56:08 AM
References
Acia Anat 1991;140:369-372
Adrenergic Nerve Fibers in the Human Fetal Sciatic Nerve1 ./. Koistinaho Laboratory of Gerontology. Department of Public Health. University of Tampere, Finland
KeyWords. Human • Sciatic nerve • Adrenergic • Neuropeptide Y • Endoneurium • Epiperineurium • Development
Introduction The peripheral nerve receives adrenergic innervation [Appenzeller et al.. 1984; Dhital et al., 1985; Rechthand et al., 1986; Koistinaho et al., 1989]. A dense adrenergic network has been found around epiperineurial arterioles in the sciatic and vagal nerves of the rat and rabbit. Single adrenergic nerve fibers have also been observed in the endoneurium, occasionally contacting capillaries | Recht hand et al., 1986; Koistinaho et al.. 1989]. In addition, serotonin | Appenzeller et al.. 1984] and some neuropep tides. e.g. substance P, vasoactive intestinal peptide [Appenzeller et al., 1984]. neuropeptide Y (NPY) and calcitonin-gene-related peptide [Dhital and Appenzeller. 1 This study was financially supported by the Finnish Cultural Foun dation of Pirkanmaa.
1988], are neurotransmitters found in association with blood vessels in the epiperineurium of the rat. guinea pig or rabbit peripheral nerves. Although the perivascular innervation in the epiperi neurium and endoneurium of the peripheral nerve is rel atively well described in rodents and the monkey [Hara and Kobayashi. 1987]. there has been limited investiga tions of the perivascular innervation in the human periph eral nerve. Using electron microscopy, Grover-Johnson et al. [ 1981 ] found perivascular nerve profiles around epineurial arterioles in the human sural nerve. They also reported that the number of perivascular axons was decreased in the epincurium of the diabetic sural nerve. However, there have been no studies exploring the trans mitter nature of the innervation of the microvessels in the human peripheral nerve, or aiming to determine whether adrenergic nerve fibers also exist in the endoneurium.
Downloaded by: Temple University 155.247.166.234 - 1/7/2020 10:56:08 AM
Abstract. The adrenergic ¡nervation was studied in the human sciatic nerve at the gestational age of 16. 17.18 and 21 weeks. Formaldehyde-induced catecholamine fluorescence, tyrosine hydroxylase (TII) and neuropeptide Y (NPY) peroxidase-antiperoxidase immunohistochemistry methods were used. At the gestational age of 16.17 and 18 weeks no adrenergic or NPY-positive nerve fibers were seen. At 21 weeks both fluorescence microscopy and TH irnmunohistochcmistry showed adrenergic nerve fibers around arterioles in the epiperineurium and single nerve fibers in the endoneurium not related to blood vessels. The number of adrenergic nerve fibers appeared to be higher in the sciatic than in the tibial segment of the nerve. At this age, as at earlier stages of gestation, no NPY-positive nerve fibers were seen either in the epiperineurium or in the endoneurium. The results suggest that adrenergic nerve fibers may be associated with the epiperineurial blood vessels in the human sciatic nerve, and that the innervation starts to develop between 18 and 21 weeks of gestational age.
370
Therefore, it was interesting to study the adrenergic and NPY-ergic innervation in the human fetal sciatic and tibia! nerves.
Material and Methods Normal human fetuses were received from legal interruptions of pregnancy. The gestational age of the fetuses ranged from 16 to 21 weeks. A total of 12 sciatic nerves were studied. Within 3 h of delivery, the nerves were dissected out and immersed either in liquid nitrogen or in 4% formaldehyde. The frozen samples were freeze-dried and pro cessed according to the formaldehyde-induced fluorescence method [Koistinaho et al.. 1989]. The formaldehyde-fixed samples were pro cessed according to the original peroxidase-antiperoxidase immunohistochemistry technique [Sternbcrgcr. 1979| using tyrosine hydroxy lase (TH) (EugeneTechnics. Allendale. N.J.. USA)and NPY (Milab. Sweden) antibodies, diluted 1:100 and 1:300. respectively. The sec tions were viewed using an Olympus Vanox T light and fluorescence microscope.
Results In the sciatic nerves from fetuses at 19 weeks of gesta tional age and younger, no adrenergic nerve fibers were seen by fluorescence microscopy. TH and NPY immunohistochemistry also gave negative results. In the sciatic nerve from the fetuses at 21 weeks of ges tational age, fluorescence microscopy showed adrenergic nerve fibers both in the epiperineurium and in the endoncurium (fig. 1-3). The number of nerve fibers appeared to be higher in the proximal than in the distal part of the nerve. In the epiperineurium. adrenergic nerve fibers were always associated with arterioles or arteries of varyingsize. In the cndoncurium. adrenergic nerve fibers were usually not found contacting blood vessels. TH-like immunoreactivity corresponded to the adren ergic nerve fibers seen in fluorescence microscopy, but the intensity of the staining varied and was weaker in the endoneurium than in the epiperineurium (fig.4). On the other hand. NPY-likc immunoreactivity was found nei ther in the perivascular nerve fibers, nor in the epiperi neurium. nor in the endoneurium.
Discusssion Perivascular adrenergic nerve fibers in the human sci atic nerve were observed first in 21-week-old fetuses. In previous studies on human fetuses, fluorescent adrener gic nerve fibers were first observed in the gut at 10 weeks
|Rcad and Burnstock, 1970], in the eye at 8-10 weeks [Ehingcr and Sjoberg, 1971], in the heart at 16-18 weeks |K anervaet al.. 1974] and in the pial vessels at 15 weeks [Nobin and Bjorklund. 1973] of gestational age. Our results are in agreement with the suggestion that, in humans, the development of adrenergic innervation is slower in the cardiovascular system than in other organs, e.g. in the gastrointestinal tract [Kanerva et al.. 1974]. In the human sural nerve, blood vessels are absent up to 17 weeks of gestational age, and are first observed 1 week later in the epiperineurium [Ochoa. 1971]. Since adrenergic nerve fibers are associated with the arterioles and arteries in the epiperineurium of human and rodent peripheral nerves [Grover-Johnson et al.. 1981; Rechthand et al.. 1986: Koistinaho et al.. 1989], the appearance of blood vessels in the fetal nerve may be required before adrenergic nerve fibers are able to grow in the epiperineurium. Stimulation of lumbar sympathetic ganglia reduces nerve blood flow, constricts epiperineurial blood vessels and closes endoncurial capillaries in the rabbit sciatic nerve [Lundborg. 1970; Selanderet al.. 1985]. indicating that adrenergic nerve fibers play an important role in con trolling blood flow in the normal peripheral nerve. As adrenergic nerve fibers were present in the epiperineu rium and endoneurium in the sciatic nerve of a 2 1-weekold fetus, it is likely that adrenergic nerve fibers also have a role in controlling blood flow in human nerves. Since synapses are usually found 2-3 weeks after nerve fibers have developed in the human autonomic nervous system |Kanerva et al., 1974]. adrenergic nerve fibers in the human sciatic nerve may become functional as early as at 23-25 weeks of gestational age. TH immunohistochemistry has been used as a marker for adrenergic neurons and nerve fibers in adult and fetal tissues [H ervonenetal., in press; Jarvi. 1989]. Inthe pres ent study, only a few faint TH-immunoreactive nerve fibers were seen in the sciatic nerve of 21-week-old fe tuses. As catecholamines may not be liberated from nerve fibers at this stage of development, the amount and activ ity of TH arc probably very low in adrenergic nerve fibers due to low synthesis of noradrenaline. Similarly, unde tectable NPY-containing nerve fibers, which in adults may have a strong vasoconstrictive effect [Edvinsson et al.. 1987], may be explained by the immaturity of the autonomic nervous system at the age of 21 weeks in the human fetus. The number of adrenergic nerve fibers was higher in the proximal part than in the distal part of the sciatic nerve in the 21-week-old fetuses, and adrenergic nerve fibers
Downloaded by: Temple University 155.247.166.234 - 1/7/2020 10:56:08 AM
Koistinaho
Adrenergic Nerve Fibers in the Human Fetal Sciatic Nerve
371
were also found in the endoneurium not related to blood vessels. Previous studies on the peripheral nerves of the adult rat and rabbit have shown a similar distribution of adrenergic nerve fibers in the epiperineurium and endoneurium |Appenzeller et al.. 1984; Rechthand et al., 1986; Koistinaho et al.. 1989]. There is also evidence that adrenergic innervation in the peripheral nerve is altered both in experimental and human diabetes [Grover-John-
son et al.. 1981; Dhital et al.. 1985; Koistinaho et al., 1990b] and also during aging | Koistinaho et al., 1990a] and in chronic hypertension in the rat (Koistinaho et al.. 1989], Although the present study used fetal tissue, it is suggested on the basis of the similar distribution of adrenergic innerva tion in the human and rodent sciatic nerve that the rodent sciatic nerve could serve as a model in studying the peri vascular innervation in peripheral neuropathies.
Downloaded by: Temple University 155.247.166.234 - 1/7/2020 10:56:08 AM
Fig. 1-3. Fluorescence micro graphs showing adrenergic nerve fibers in the epineurium (black arrows) and in the endoneuriunt (open arrows). The nerve fibers in the epineurium arc usually associ ated with blood vessels. 1, 2 x6()(). 3 x 300. Fig. 4. Micrograph showing TIIimmunoreactive nerve fibers (black arrows) in the endoneurium. X 600.
372
Koistinaho
Appenzeller, O.: Dhital. K.K:. Cowen.T.: Burnstock, G.: The nerves to blood vessels supplying blood to nerves: the innervation of vasa nervorum. Brain Res. 304: 383-386 (1984). Dhital. K.K.: Appenzeller. O.: Innervation of vasa nervorum; in Burnstock. Griffith. Nonadrcnergic innervation of blood vessels, pp. 191-211 (CRC Press. Boca Raton 1988). Dhital. K.: Lincoln. J.: Appenzeller. O.: Burnstock. G.: Adrenergic innervation of vasa and nervi nervorum of optic, sciatic, vagus and sympathetic nerve trunk in normal and streptozotocin-diabetic rats. Brain Res. 367: 36—14 (1985). .Edvinsson. L.: MacKenzie. E.T.; McCulloh. J.; Uddman. R.: Perivas cular innervation and receptor mechanisms in cerebrovascular bed: in Day, White. Cerebral blood flow: physiological and clinical aspects, pp. 145-172 (McGraw-Hill. New York 1987). Ehingcr. B.: Sjoberg. N.-O.: Development of the ocular adrenergic nerve supply in man and guinea-pig. Z. Zellforsch 188: 579-592 (1971). Grover-Johnson.N.M.: Baumann. F.G.: Imparato. A.M.: Kim. G.E.; Thomas. P.K.: Abnormal innervation of lower limb cpiiicurial arterioles in human diabetes. Diabetologia 20: 31-38 (1981). Hara. H.: Kobayashi. S.: Adrenergic innervation of the vasa nervorum in the cranial nerves and spinal roots in the subarachnoid space. Exp. Neurol. 98: 673-676 (1987). Ilervonen. A.: Pelto-Huikko. M.: Pickel. V.M.; Reis. D J .: Joh.T.lL: Immunohistochemical localization of the catecholamine synthe sizing enzymes and enkephalin-like immunoreactivity in the human fetal adrenal medulla. Anat. Embryol. (in press). Järvi. R.: Localization of bombesin-, neuropeptide Y-. enkephalinand tyrosine hvdroxylase-like immunoreaetivities in rat coeliacsuperior mesenteric ganglion. Histochemistry 92: 231-236 (1989). Kanerva. L.: Hervonen. A.: I lervonen, H.: Morphological character istics of the ontogenesis of the mammalian peripheral adrenergic nervous system with special remarks on the human fetus. Med. Biol. 52: 144-153 (1974). Koistinaho. J.: Wadhwani. K.C.; Rapoport. S.L: Increased density of adrenergic innervation in the tibial and vagus nerves of sponta neously hypertensive rats. J. Neurosci. Res. 24: 424—43(1 (1989).
Koistinaho. J.; Wadhwani. K.C.: Rapoport. S.L: Adrenergic innerva tion of the tibial and vagus nerves in rats of different ages. Mech. Ageing Dev. 52: 195-205 (1990a). Koistinaho. J.; Wadhwani. K.C.; Rapoport. S.L: Adrenergic innerva tion in the tibial and vagus nerves of rats with strcptozotocininduced diabetes. Brain Res. 513: 106-112 (1990b). Lundborg, G.: Ischemic nerve injury. Scand J plast. Reconstr. Surg.. suppl. 6. pp. 1—46 (1970). Nobin. A.; Bjbrklund. A.: Topography of the monoamine neuron sys tems in the human brain as revealed in fetuses. Acta physiol, scand.. suppl. 388 (1973). Ochoa. J.: The sural nerve of the human foetus: electron microscope observations and counts of axons. J. Anat. 108: 231-245 (1971). Read, J.R.; Burnstock, Ci.: Development of the adrenergic innerva tion and chromaffin cells in the human fetal gut. Dev. Biol. 22: 513-534(1970). Rechthand, E.: Hervonen. A.; Sato. S.: Rapoport. S.L: Distribution of adrenergic innervation of blood vessels in peripheral nerve. Brain Res. 374: 185-189(1986). Selander. D.: Mansson. L.G.: Karlsson. L.: Svanvik. J.: Adrenergic vasoconstriction in peripheral nerves of the rabbit. Anaesthesiol ogy 62: 6-10 (1985). Sternbergcr. L.A.: Immunohistochemistry; 2nd ed. (Wiley. New York 1979).
Received: October 25. 1990 Accepted: December 20. 1990 Dr. J. Koistinaho Laboratory of Gerontology Department of Public Health University of Tampere PO Box 607 SF-33101 Tampere (Finland)
Downloaded by: Temple University 155.247.166.234 - 1/7/2020 10:56:08 AM
References
