Med. Surg. J. – Rev. Med. Chir. Soc. Med. Nat., Iaşi – 2019 – vol. 123, no. 4

SURGERY REVIEWS

GHEORGHE MARINESCU (1863-1938) AND LA CELLULE NERVEUSE. 110 YEARS SINCE WRITTING OF THE MAJOR CHAPTER OF THE OLD TESTAMENT OF NEUROPATHOLOGY

Mihaela Dana Turliuc1,2, A. I. Cucu2*, Claudia Florida Costea3, A. Mohan4,5 , A. V. Ciurea6,7 “Grigore T. Popa” University of Medicine and Pharmacy Iasi 1. Faculty of Medicine Department of Surgery (II) “Professor Dr. N. Oblu” Clinical Emergency Hospital Iasi 2. Department of Neurosurgery 3. Department of Ophthalmology 4. County Emergency Hospital Oradea, Department of Neurosurgery 5. University of Oradea, Faculty of Medicine and Pharmacy 6. “Carol Davila” University of Medicine and Pharmacy, 7. “Sanador” Clinical Hospital, Department of Neurosurgery, Bucharest, *Corresponding author. E-mail: [email protected]

GHEORGHE MARINESCU (1863-1938) AND LA CELLULE NERVEUSE. 110 YEARS SINCE WRITTING OF THE MAJOR CHAPTER OF THE OLD TESTAMENT OF NEURO- PATHOLOGY (Abstract): 110 years ago, in 1909 in , Gheorghe Marinescu's La Cellule Nerveuse appeared. The work was practically a complete and extremely rich review of the lit- erature of that time, in which Marinescu integrated the results of his own research. The book contained chapters on embryology, cytology and physiology of the nerve cell, but also on the pathology. La Cellule Nerveuse also recalls Marinescu’s pioneering studies in the field of neu- ronophagy, as well as his studies in the field of chromatolysis. Nowadays, La Cellule Nerveuse and the whole activity of Gheorghe Marinescu in the field of neuropathology have been an im- portant pillar not only for the development of the Romanian School of Neurology and Neuropa- thology, but also for the development of the European neurology that we should remember to- day. Keywords: GHEORGHE MARINESCU, NEUROPATHOLOGY, ROMANIAN SCHOOL OF NEUROLOGY AND NEURO-PATHOLOGY, NERVOUS CELLS.

HISTORICAL DATA to both the Faculty of Medicine and the The founder of the Romanian School of School of Bridges and Roads. Neurology and Neuropathology, Professor After the first year, he will remain only Gheorghe Marinescu (1863-1938) (fig. 1), at the medical school, where he will work was born on 23rd of February 1863 in Bucha- as a student in the newly founded histology rest. In 1874 he was enrolled by his mother at laboratories by Professor Petrini-Galatz, the Central Orthodox Seminary, which he the first head of the Department of Histolo- completed the second of his promotion. Re- gy of the Faculty of Medicine in Bucharest. fusing the mother's desire to continue his Later, in 1886 he became assistant in this theological studies, young George is admitted laboratory and intern of the Brancovenesc

676 Gheorghe Marinescu (1863-1938) and La cellule nerveuse. 110 years since writing of the major chapter of the old testament of neuropathology

Hospital from Bucharest (fig. 1) (1). president of the League of Medical Stu- He was Professor Victor Babes’ assis- dents and by a letter of recommendation tant, within the Institute of Bacteriology signed by several teachers including Victor (2). He became his disciple and they col- Babes, he was admitted to a scholarship for laborated together on the Atlas of Patho- a period of nine years at the Salpêtrière logical Histology of the Nervous System Hospital in Paris (fig. 2), where he will (3). In 1889, the young George was elected study neurology (2).

Fig. 1. Professor Gheorghe Marinescu (1863-1938) (a). Brancoveanu Hospital, Bucharest (b) (public domain)

Fig. 2. Jean Martin Charcot (1825-1893) (a). A Clinical lesson at the Salpêtrière (with Prof. Charcot and others) (1887), André Brouillet (1857-1914), Paris Descartes University, Paris (b) Marinescu is missing from the painting, because he arrived at the Salpêtrière in 1889, two years later (public domain).

677 Mihaela Dana Turliuc et al.

At that time, the famous hospital was Nerveuse (The Nervous Cell) (3), in which led by Jean-Martin Charcot (1825-1893) he postulated that: evolution and involution (fig 2), the founder of modern neurology. of neurons depend on active oxidation (5). About Charcot, later in 1925 Marinescu In this book he wrote about the cell biology noted: I had the opportunity to meet per- of the neuron and its organelles, such as sonally not only the most renowned neurol- neurofibrils, pigments, Nissl bodies, the ogists contemporaries, but also great sci- nucleus and nucleoli, both in the normal entists, such as R. Virchow, R. Koch, P. and the pathological status of the nerve Ehrlich. Neither one made an impression cell. Although his work in this field of as profound as Charcot, an impression that neuropathology has been extensively de- remains alive in my soul (4). scribed and published in this book, he did Marinescu remained a volunteer assis- not stop to work and continued until his tant at Salpêtrière and collaborated with death in 1938 (2). (1853-1940), Gilles de la Tourette (1857-1904), Paul Oscar Blocq THE MAIN NEUROPATOLOGICAL (1860-1896) and (1857- WORK: THE NERVOUS CELL 1932) (5). He also traveled to different La Cellule Nerveuse (fig. 3) was practi- universities in Europe, where he met and cally a complete and extremely rich review studied with Carl Weigert (1854-1904) in of the literature of that time, in which and Emil du Bois-Reymond Marinescu integrated the results of his own (1818-1896) in (1, 3, 5, 6). research (2), being the first book of its kind After defending his doctoral thesis in in the world, greeted with enthusiasm by Paris, The Succulent Hand in Syringomye- scientists like Santiago Ramón y Cajal lia, Marinescu returns to Bucharest where (1852-1934) and it has not been surpassed he was appointed as Chief doctor at Pan- until today by any such work. This was due telimon Hospital in May 1897 (6). For a to the fact that Marinescu did not study the period of more than 20 years he traveled fixed and colored nerve cell only under the daily around 12 km to the hospital, until microscope, but also investigated it in the the Neurological Clinic was transferred to living state (4). the Colentina Hospital (4). In volume I, Marinescu presents the At Pantelimon Hospital, together with general morphology of the neuron with all his first intern, Constantin I. Parhon (1874- its components known at that time using 1969), he reorganized the service starting optical microscopy and fixation and stain- with new laboratory researches in the field ing techniques (7). He reviewed in detail: of neuropathology. One month later, in July nucleus and nucleoli, Nissl bodies, centro- 1897, at the age of 34, Marinescu becomes some, neurofibrils, Golgi apparatus, bio- the first Head of the Department of Neu- blasts of Altmann (e.g. mitochondria) and rology of the Medical Faculty of Bucharest the colored granules (black pigment for (6). locus niger and locus coeruleus, as well as Marinescu's main area of interest was yellow pigment) (2, 7). neuronal pathology, and his observations Regarding neurofibrils, Marinescu con- and hypotheses were published in 1909 in sidered that they are inserted at the periph- Paris, in his monograph La Cellule ery of the cell and at the wall of the nucleus,

678 Gheorghe Marinescu (1863-1938) and La cellule nerveuse. 110 years since writing of the major chapter of the old testament of neuropathology naming this structure spongioplasma. He impulse. He was also convinced that: was also the first to conclude that spongio- chromatophilic elements represent a sub- plasma lesions can lead to degeneration of stance with high chemical potentials, which peripheral extensions of the nerve cell (8). is the place of a continuous phenomenon of Regarding the role of the chromato- integration and disintegration, and through philic elements, Marinescu considers that these phenomena the nerve cell becomes an they conducts the nervous impulses and energetic device (translation of the authors) furthermore, the large chromatophilic ele- (1). He also named these structures, generi- ments influence the intensity of the nerve cally, under the term kinetoplasma (9).

Fig. 3. La Cellule Nerveuse, published by G. Marinescu in 1909 (7) (a). Transversal section of a histological preparation showing the nervous fibrils. Chick embryo at six days of incubation. f – ventral roots, gs – spinal ganglion, rp - dorsal root (adapted after Le Cellule Nerveuse (G. Marinescu, 1909) (7) (b) (public domain).

Regarding the paranuclear corpuscles, dedicated to neuroembryology (7), in which small acidophilic inclusions present in the he reviews the knowledge of the time on this nuclei of pigmented neurons of the sub- subject, to which he adds personal observa- stantia nigra and locus coeruleus, tions that do not depart from the vision of Marinescu also described them in humans some of his mentors: Santiago Ramón y (10) (later named Marinesco bodies). He Cajal and Wilhelm His (1863-1934). One of also found that they are more abundant in the theories involved the existence of two adults and elderly compared to young peo- types of cells in the neural tube or neuroepi- ple, and also absent in children (7). thelium: the germ cells that Marinescu con- An entire chapter of the first volume was siders neuronal precursors and the epithelial

679 Mihaela Dana Turliuc et al. cells that will generate the glial support. by Santiago Ramón y Cajal (3), who wrote a Marinescu's neuroembryology studies were laudatory preface: honorable colleague and largely based on chicken embryos, mice or learned friend, Professor Marinesco is also even human embryos and fetuses (2). In an insightful observer and a strong and addition, Marinescu also noted in his work tenacious supporter of the experimental that all neurons are not born at the same method and that his activity is undeniable, time, a phenomenon now known as a tem- his fruitful research in the difficult field of poral gradient of differentiation (2). the histology of the nervous system has The second volume of La Cellule earned him a reputation and authority more Nerveuse contained Marinescu's contribu- than enough to impose his own book on the tion to the histopathology of the nervous attention and praise of the learned world system and in which he focused on two (translation of the authors) (7). entities considered to be important for the Professor Marinescu died in 1938 and neuropathology field: chromatolysis and on his tombstone is written: Work ... Sin- neuronophagia (2, 8). He differentiated cerity .... Silence .... (1). He remained for between the central chromatolysis that the Romanian medicine as the founder of appeared in the cell body of the neuron the School of Neurology, and his entire after axon sectioning and the peripheral work together with La Cellule Nerveuse chromatolysis that could be observed in was an important pillar in the development primary lesions of the nerve cell produced of European neurology, which we should by traumatic or toxic causes (2). remember today. In his experimental studies in rabbits, At the turn of 156 years since his birth, Marinescu also made observations on cell 81 years after his death and 110 years since injuries secondary to nerve sectioning. In the publication of the La Cellule Nerveuse other experiments on small animals such as (1909), we wonder what is today's the in- guinea pigs, cats or frogs, he also observed heritance of Gheorghe Marinescu. Of that trauma of the nerve centers leads to course, his name is closely related to the initial necrosis and that the neurons do not succulent hand in syringomyelia, to the regenerate, while blood vessels and neurog- Marinesco-Sjögren syndrome, to the first lia proliferate (2). descriptions of lesions in the niger locus of Professor Marinescu was also a pioneer Parkinson's disease (2), to the more than in the field of neuronophagia, concluding 1500 works in the field of neuroanatomy, after multiple studies of chromatolysis and neuropathology, neurophysiology, histo- granular fibrillary degeneration, that oxida- chemistry (12), but especially because of tive stress is a major contributor to the his monumental work in the field of neuro- process of neuronal aging (3). He intro- cytology and neuropathology of the nerve duced the term neuronophagia and demon- cell and his studies in the field of chroma- strated that phagocytes are not glial cells, tolysis and neuronophagia - La Cellule but mesoderm-derived mobile cells located Nerveuse (2). near the neuron or migrating from the In 1951, the anatomist Murray Barr said blood vessels. Later, he assimilated them that La Cellule Nerveuse, together with with microglia (11). Cajal’s better known Histologie du Système The Nervous Cells’s preface was written Nerveux de l’Homme et des Vertébrés, are

680 Gheorghe Marinescu (1863-1938) and La cellule nerveuse. 110 years since writing of the major chapter of the old testament of neuropathology major chapters in the neurocytologist’s Old world from which no one has returned, I Testament (13). would not upset anyone, but the truth must Beyond these, Marinescu has left us a be said: too much injustice is in the blessed legacy of humanity. During World War I he country of ! It is due to the ease or offered himself as a volunteer at the Salpê- haste with which the vital problems of the trière Hospital in Paris, where he cared of homeland were solved. The lack of true wounded soldiers with Pierre Marie. Later, citizenship education and the feeling of for his humanitarian sacrifice, the French duty, as well as immense pride or some government granted him the title of “Of- passing ambitions have given rise to many ficer of the Legion d'honneur” (5). social anomalies (14). Three days before his death, Professor Marinescu wrote his own testament in CONCLUSIONS which he mentioned: No flower, no speech; Gheorghe Marinescu represents a Euro- those who loved me used the money for pean and international personality in the poor children and good words to encour- field of neurology and neuropathology. His age the suffering. Do not forget that those works together with those of Ramon Y who are living in poverty and even in mis- Cajal (1852-1934) represent the fundamen- ery are too numerous, that those with mon- tal element in the development and under- ey, those who are enriched by neon means standing of the neurological sciences. In live from the exploitation, in one way or this domain, the keystone is his work pub- another, of those who work. Leaving for the lished in , 110 years ago.

REFERENCES

1. Mohan A, Marinescu AA, Cotirlet A, Saceleanu V, Ciurea AV. Remember Gheorghe Marinescu (1863-1938). Proc Rom Acad Series B 2018; 20(2): 149-154. 2. Catala M, Poirier J. Georges Marinesco (1863-1938): neurologist, neurohistologist and neuropa- thologist. Rom J Morphol Embryol 2012; 53(4): 869-877. 3. Barboi A. Gheorghe Marinescu (1863-1938). J Neurol 2005; 252: 114-115. 4. Radu I, Musat C, Gabrean S. Gheorghe Marinescu, savant de renume mondial. Repere iatro-istorice. JMB: 2008; 42-45. 5. Ionita C, Fine EJ. A Romanian neurologist and neurophysiologist. J Hist Neurosci 2003; 12(2): 206. 6. Bistriceanu I. Viata si opera profesorului Dr. G. Marinescu. Bucuresti: Cartea Medicala, 1924. 7. Marinesco G. La cellule nerveuse, vol. 1, Paris: Octave Doin et fils, 1909. 8. Marinesco G. La cellule nerveuse, vol. 2, Paris: Octave Doin et fils, 1909. 9. Marinesco G. Recherches sur la structure normale et pathologique de la microglie, 1930. In: ***, Oeuvres choisies (1963), vol. II, Paris: Masson, Paris, 1897. 10. Marinesco G. Sur la presence des corpuscles acidophiles paranucleolaires dans les cellules du locus niger et du locus ceruleus. Paris: CR Acad Sci 1902; 135: 1000-1002. 11. Marinesco G. Pathologie de la cellule nerveuse, Rapport présenté au Congrès international de méde- cine tenu à Moscou du 19-26 août 1897, Paris: Georges Carré C. Naud éditeurs, 1897. 12. Marinesco M, Petresco A, Marinesco G. Georges Marinesco et la France. Histoire des sciences médi- cales 1984; 18: 13-18. 13. Barr ML. La cellule nerveuse. Science 1951; 114(2956): 215-216. 14. Marioara G. Marinescu, G. Brătescu. Corespondenţă (1889–1938). Bucuresti: Editura Ştiinţifică, Colecţia “Savanţi de pretutindeni”, 1968.

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