Keywords: Microscopy - Nervous System - Cerebral Cortex
Palavras-chave: Microscopia - Sistema Nervoso - Córtex Cerebral
INTRODUCTION
The study of anatomy has aroused the interest of innumerous researchers since the
far antiquity, and gross features were revealed through dissection of varied classes
of animals, and also, in some periods, of human corpses[1 ],[2 ]. The advent of the microscope permitted to expand the anatomic findings with the
study of the fine structure of tissues and organs[3 ]. Among the researchers who pioneered such studies, the name of the Italian physician,
biologist, botanist, and anatomist Marcello Malpighi (1628-1694), later seen as the
“founder of microscopic anatomy” (histology), must be stressed[4 ] ([Figure 1 ]).
Figure 1 Marcello Malpighi (author LC Miall).Public domain. Available at: https://commons.wikimedia.org/wiki/File:MarcelloMalphigiMiall.jpg
MALPIGHI’S CAREER
Malpighi obtained the degree of Philosophy and of Medicine (1653), and became successively
Professor of Medicine at the Universities of Bologna, Pisa, and Messina. He was introduced
to the microscope while in Pisa (1656), being apparently one of the first to use the
compound instrument (objective plus ocular lenses), turning possible much of his research.
He moved to Rome after accepting the invitation to be Pope Innocent XII personal physician
(1691)[4 ],[5 ],[6 ], where he also taught Medicine in the Papal Medical School, and continued treating
patients, in person and by post[6 ],[7 ]. He authored many important scientific contributions on the structure of animals,
describing varied tissues and organs, as the liver, brain, lung and pulmonary circulation
(with the discovery of the capillaries), heart, kidney, spleen, skin, tongue, and
many of his findings would later carry his name. Additionally, he studied the chick
embryo development, insects, and plants[8 ]. His microscopic findings on the nervous system were novel and important, and here
some aspects will be highlighted.
THE NERVOUS SYSTEM
Malpighi’s investigations on the nervous system were first published in De Cerebro Epistola (1665)[9 ]. Next, he presented in De cerebri cortice (1666) a more detailed description of the microscopic structure of the nervous system,
with emphasis on the “cortex of the cerebrum” (cerebri cortice ) [cerebral cortex], apparently for the first time[10 ],[11 ],[12 ]. The studies were performed through sections of material of various classes of vertebrates,
and the findings resulted from dissection, and microscopic examination[9 ],[10 ].
His initial account was on the general anatomic aspects of the nervous system of “perfect
animals” (higher animals [mammals]), as known at the time[9 ],[10 ],[11 ]. However, his main target was to know the minute composition of these structures
“…to acquire a better knowledge of the smallest structures of this substance [nervous
tissue] …up to now unclear…”[10 ],[12 ],[13 ]. He reported that the cerebral cortex was constituted by a collection of tiny “glands”
(“cells” -“nerve cells”) with an oval shape, some forming obtuse angles when compressed
by adjacent elements (glands). They were connected to roots of white nervous fibers,
like special vessels, analogous to the excretory canals of true glands. The cortical
substance (gray matter - glands) was also found inside the cerebral ventricles (basal
nuclei), in the beginning of the spinal medulla (medulla oblongata) (brain stem),
in the external sheet of the cerebellum, scattered in many places under the pons of
Varolius, and inside the entire spinal medulla (spinal cord). He described also the
already better-known fibers that formed the white matter (1666)[10 ],[12 ],[13 ],[14 ] ([Table 1 ]).
Table 1
Excerpts of Malpighi’s microscopic description of the nervous system[10 ],[12 ],[13 ],[14 ].
•The studies were performed through sections of material of sanguineous perfect animals
[perfectorum animalium ] (higher animals [probably mammals]), larger fishes, and other classes of vertebrates.
The findings resulted from dissections of cooked material, eventual pouring of ink
and then lightly wiping away, and microscopic examination.
•Regarding the [cerebral] gray matter, he reported: “…in the brain of perfect animals
the cerebral cortex is formed by a collection of tiny glands [nerve cells], found
in the cerebral gyri…”. And: “They have an oval shape, but, as they are compressed
by adjacent [glands], some form obtuse angles…”. Then: “Their external portion is
in contact with the pia mater and its blood vessels, which penetrate from above into
their substance…the interior part gives off white nervous fibers, like special vessels,
analogous to the excretory canals of true glands…”. And more: “…the medullary matter
[white matter] is a result of the assemblage of many kinds of small [nervous] fibers
jointed together…”. Further: “These cortical glands…make up the external cerebral
gyri and are connected with the medullary fibers which take their origin from them,
in such a way that, wherever gyri are cut transversely, a fixed and constant mass
of glands is surrounding the white matter…observed more clearly in the cerebellum…”
•Describing deeper structures: “…the cortical substance [gray matter] inside the cerebral
ventricles [prominences of the ventricles] [basal nuclei] is of the same nature as
that of outside of the brain [i.e., glands], and the same is also seen in the beginning
of the spinal medulla…”. And: “Inside of the entire spinal medulla [spinal cord] the
cortical matter [gray matter] already described maintain the glandular structure,
and…under the pons of Varolius… such cortical glands are scattered in many places…”.
Further: “This also happens in the cerebellum, where the nerves leaving the pons of
Varolius, and entering inside the cerebellum, have also their origin in glands of
the cortical matter found there…”.
•About fiber tracts: “The spinal medulla is a fascicle of nerves that on attaining
the cerebrum is divided into two parts, turning smoothly to form the lateral aspects
of the ventricles...they end in the cortical matter where the extremities of the roots
are inserted in the small grains of its glands…”. And: “…in the cerebrum and cerebellum,
white fibers are seen by which the white matter is formed…they serve as vehicles of
the nervous juice (succus nervosus )…an intimate connection and continuation between these cortical glands and nervous
fibers is observed...”.
There is no illustration of the described nervous system in his De cerebri cortice . A drawing of the cortex, according to Malpighi’s description, may be found only
in Govard Bidloo’s Anatomia humani corporis (plates drawn by Gérard de Lairesse) (1685) (Table X, [Figure 2 ] from Bidloo's book)[13 ],[15 ] ([Figure 2 ]).
Figure 2 Drawing of the cerebral cortex (From Bidloo G. Anatomia humani corporis , 1685 (Table X, [Figure 2 ] from Bidloo's book)[15 ] as described by Malpighi[12 ],[13 ].A: part of boiled brain; B: meninges wrapping the brain; C: Blood vessels; D: their
capillary distribution & reticular plexus; E: various rows of cortical glands; F:
tubules (nerve fibers or vessels) assembled in fasciculi, constituting the medulla
[white matter]; G: lobular fascicles, or separations; H: complicated tubules (vessels)
(nerve fibrils); I: nerves. [F+H+I= white roots of nerves][13 ],[15 ].
COMMENTS
Malpighi provided the first microscopic description of the central nervous system
of “perfect animals" (superior animals [probably mammals]). He focused on the gray
matter, defined as “cortical”, in the various levels of the nervous system. There
he identified microscopic discrete elements he denominated “glands” in the gray matter
of the cerebral and cerebellar cortex, basal nuclei, brain stem, and spinal cord.
The fibrous structures, he called “nerve fibers” (or vessels, or excretory ducts),
were constituents of the already known subcortical white matter and tracts. His interpretation
of the cortical elements as “glands” may be related to his admiration for Hippocrates,
who regarded the brain as a glandular organ (Cerebrum inter glandulas recenset , as he wrote, based on De GIandulis ), to a homology to other organs he identified as glandular (e.g., liver)[12 ], and supporting a presumed glandular function of the cortical matter (cerebral and
cerebellar cortex), responsible for filtering the blood to produce “nervous juice”
(animal spirit), carried by nerve fibers (vessels) [ducts] coursing downward (to the
medulla oblongata and spinal cord) (in accordance to Thomas Willis view)[12 ],[13 ],[16 ]. It is important to highlight that at the time, although the term “cell” was already
known, due to Robert Hooke’s studies (1665), the concept of “cell” was introduced
much later, by Theodor Schwann and Matthias Schleiden (1839), while the concept of
“nerve cell” was yet unknown, beginning to appear only in the second half of the 19th century, mainly thanks to Jan Evangelista Purkinje, describing “ganglionic bodies”
in the gray matter of the brain (1837)[3 ],[17 ].
The microscopic findings of the cortical matter (the glands) generated adverse arguments,
frequent at his time, and more recently some authors claimed, mainly in relation to
the nervous system, that they represented artefacts[4 ],[13 ],[18 ]. Others accepted that they represented valid structures[10 ],[13 ],[18 ]. It should be considered that the recent criticism was mostly directed to the drawing
of the cerebral cortex, and less to the original description. It must be remembered
that the real author of this depiction remained undefined, and that probably it was
drawn based on Malpighi’s description, and not from direct observation of the specimen
under the microscope[13 ]. Curiously, such debate was only directed to the findings of the cerebral cortex,
and not to the other levels, neither to the observations of other tissues and organs,
studied with the same precarious methods, which were, on the contrary, praised[13 ].
It can be affirmed, without error, that Malpighi’s findings, identifying minute elements
in the gray matter of the nervous system, an unshaped tissue until his time, was a
large new step to elucidate its structure. Following Malpighi, many researchers performed
microscopic examination of the nervous system. However, all their reports looked unremarkable
compared to Malpighi's description. His view and the representation of the cerebral
cortex were afterwards reproduced by many authors, until the beginning of the 19th century, when new histological processing and staining techniques appeared, as well
as improved microscopes[3 ],[13 ].
