Серое вещество это аксоны или дендриты

General Features

IMAGING

Dynorphin Expression in the Central Nervous System and Possible Biological Actions

Initial immunocytochemical studies of dynorphins were carried out in the rat hypothalamus, where Dyn (1–13) was found to be colocalized with vasopressin in magnocellular neurons of the supraoptic and paraventricular nuclei.¹⁷ The immunocytochemical distribution of peptides derived from the prodynorphin precursor in the brain of the rhesus monkey (Macaca mulatta) indicates a widespread neuronal localization of immunoreactivity from the cerebral cortex to the caudal medulla. Immunoreactive perikarya are located in numerous brain loci, including the cingulate cortex, caudate nucleus, amygdala, hypothalamus, thalamus, substantia grisea centralis, parabrachial nucleus, nucleus tractus solitarius, and spinal cord dorsal gray laminae. In addition, fiber and terminal immunoreactivity are seen in varying densities in the striatum and pallidum, substantia innominata, hypothalamus, substantia nigra pars reticulata, parabrachial nucleus, spinal trigeminal nucleus, and other areas. The distribution of prodynorphin peptides in the brain of the monkey is similar to that described for the rat brain; however, significant differences also exist. In situ hybridization histochemistry has been adopted as a technique to investigate the localization of prodynorphin mRNA in the central nervous system; this approach has confirmed that prodynorphin-containing cells are relatively widespread throughout brain regions that contain dynorphin peptides.¹⁷

Dynorphins play a role in a wide variety of physiological parameters, including motor activity, cardiovascular regulation, respiration, temperature regulation, feeding behavior, and hormone release.²⁵ Although they do not elevate pain threshold when injected in the brain, they antagonize opioid analgesia in naive animals and potentiate it in tolerant animals. Dynorphins have beneficial effects on stroke that are like those of opioid antagonists rather than like those of agonists.²⁹

Prodynorphin-positive neurons are widely distributed in brain and spinal cord areas involved in the transmission of nociceptive stimuli.¹⁷ Dynorphins may be involved in a local circuit within the spinal cord, and in supraspinal functions. Interestingly, dynorphins were also detectable in cutaneous nerves with a distribution similar to that of calcitonin-gene-related peptide, a specific marker for sensory neurons. A moderate density of KOR binding sites has been seen in the central and peripheral neuronal nociceptive system and in various immune cells.¹⁴ A lack of an antinociceptive action of dynorphin after its administration into the lateral brain ventricle²⁴ and some slight antinociceptive activity after intrathecal injection^24,29 have been reported. Other KOR agonists also possess some antinociceptive activity after their intrathecal administration. However, the effect is much weaker on a molar basis than that evoked by MOR or DOR agonists. On the other hand, in electrophysiological experiments in spinalized rats, KOR agonists reduce reflexes stimulated by thermal and mechanical nociceptive stimuli to the same extent and in a dose-dependent manner.^20,24 Dynorphin-mediated analgesia has been ascribed to its inhibitory action on neurons at KOR. Electrophysiological evidence supports a KOR-mediated inhibitory effect of dynorphins on synaptic transmission of nociceptive neurons in the spinal dorsal horn.²⁴ Dynorphins, and other neurotransmitters, can be released and can induce the hyperpolarization of neurons, potentially through a KOR-coupled enhancement of potassium conductance. In addition, dynorphin-mediated activation of KOR suppresses calcium currents and calcium-dependent secretion.⁴ Further, dynorphin has been shown to inhibit substance P release in the spinal cord in a KOR-mediated manner.²⁰ The endogenous dynorphin–KOR system has been suggested to elicit antinociception during inflammation, pregnancy,²⁴ and acupuncture.¹² These studies support an antinociceptive function of dynorphin by negatively modulating transmission of nociceptive information.

6 The avian brain organization and circuits involved in TI

A new perspective on the neural basis of TI emerges in studies carried out in birds.

In a comparative immunocytochemical study in mice and finches species, Kingsbury et al. (2011) have given support to the “folded open hypothesis,” assuming that the avian midbrain central gray is organized much like a folded open mammalian PAG, mediolaterally oriented rather than dorsoventrally as in mammals.

According to these characteristics of avian brain organization, Melleu et al. (2017) investigated the effects of TI elicitation on c-Fos expression in adult pigeons (Columba livia), at the level of CG-ICO mesencephalic complex. In the comparison with control animals submitted to 5 min manipulation, TI elicitation induced an increase in c-Fos expression in different areas: at the SGPd of the optic tectum, at MLd and at medial and lateral ICO nucleus. On the contrary, the medial part of the nuclear complex, i.e., CG, equivalent to the mammalian ventral PAG, was not affected by TI, as proved by the absence of c-Fos response (Melleu et al., 2017).

In birds, the dorsomedial ICO area, partly comparable to the dorsal part of the mammalian PAG, is known to be involved in alarm calls in domestic chicks (De Lanerolle and Andrew, 1974) and in defense responses in some finches species (Kingsbury et al., 2011). In the latter experiments, carried out in finches and in territorial song birds (waxbill), an increased c-Fos in this region was associated with other forms of defensive behavior such as escape from human hand and subordination (Kingsbury et al., 2011).

As for the SGPd, in which c-Fos was increased after TI (Melleu et al., 2017), it is to be considered that this area, comparable either to mammalian dorsolateral PAG or to the deeper layers of the superior colliculus, is the source of tectopontine and tectobulbar descending reticular pathways that affect eye, neck and limb motor circuits that may be critical for TI development (Reiner and Karten, 1982).

Another interspecies difference in response to TI concerns the involvement of the collicula: as proved by c-Fos activation, in guinea pigs the superior colliculus, but not the inferior colliculus (Vieira et al., 2011) is affected, whereas in pigeons the TI-associated increase in c-Fos was found in MLd, i.e., the midbrain auditory nucleus, comparable to the mammalian inferior colliculus (Melleu et al., 2017). It could be suggested that, for TI mechanisms, the auditory information is more relevant in birds and the visual information more important in mammalians. The authors, underlining the differences between birds and mammals, advance the hypothesis that the pigeon’s brain organization may represent a species-specific characteristic for the circuits involved in TI mechanisms (Melleu et al., 2017).

ESSENTIAL INFORMATION

Visual rating scales

As with atrophy of the medial temporal lobe, WMH are most commonly evaluated using visual rating scales and volumetric analyses. These methods possess the same general limitations as the atrophy scales discussed earlier, although additional caution is needed when considering the locations used to assess WMH (eg, periventricular white matter, deep white matter, gray-white junction) (for full reviews see Scheltens and colleagues⁴⁹ or Kapeller and colleagues⁵⁰). The Leukoaraiosis scale (LA)⁵¹ assigns a score between 0 (no hyperintensities) and 4 (>75% hyperintensities) within 5 general regions within each hemisphere. These values are then combined to obtain a total score. Libon and colleagues⁴¹ have used this scale extensively within the context of small vessel–based vascular dementia, and the authors previously reported differences in temporal-order memory in patients with high versus low LA scores.⁵² Fazekas and colleagues’⁵³ scale uses a 4-point system to rate periventricular hyperintensities (PVH) and deep white matter hyperintensities (DWMH) separately. This scale has been widely used, but only provides general information about the presence of WMH and little information regarding the distribution of WMH.⁵⁴ Scheltens and colleagues⁵⁴ extended the Fazekas scale to include subcortical hyperintesity ratings as well as the number, size, and location of the WMH. Although this scale provides a greater breadth of information, it is time consuming and applicable only to higher-quality MRI scans.

Traumatic brain injury

Traumatic brain injury (TBI) is a significant problem in elderly patients, causing more than 80,000 ED visits per year.⁶⁷ The leading causes of TBI in elderly patients are falls, accounting for 81% of all elderly patients’ hospital visits for TBI, followed by blunt head strikes and motor vehicle crashes. Elderly patients suffering a TBI have the highest rates of hospitalization and death,⁶⁸ and older age has long been recognized as one of the more important factors predicting worsened outcomes from TBI.⁶⁹

The workup of patients presenting with TBI differs based on the mechanism, severity, and patient’s age. All patients presenting with moderate to severe TBI should undergo immediate head CT. For patients presenting with mild TBI, 3 common decision rules have been derived and are used to identify which patients should undergo head CT. All 3 studies excluded patients older than 60 or 65 years due to a higher rate of intracranial abnormalities in this patient population.^73–75 Brain imaging by head CT should be obtained in all elderly patients presenting with TBI, regardless of the severity of injury or the clinical presentation.

Like ICH, special attention must be paid to the patient on anticoagulation who suffers a moderate to severe TBI with associated intracranial hemorrhage. Medication-related coagulopathy is common in the geriatric population and increases the risk of post-TBI hemorrhage. In cases of TBI hemorrhage complicated by medication-related coagulopathy, the offending drug should be discontinued and medical management should be targeted to normalize hemostasis and avert hematoma expansion (as reviewed in detail in ICH section and Table 1).^51,52